Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger

OBJECTIVE: A prospective multi-institutional randomized surgical trial involving 740 stage I and II melanoma patients was conducted by the Intergroup Melanoma Surgical Program to determine whether elective (immediate) lymph node dissection (ELND) for intermediate-thickness melanoma (1-4 mm) improves survival rates compared with clinical observation of the lymph nodes. A second objective was to define subgroups of melanoma patients who would have a higher survival with ELND. METHODS: The eligible patients were stratified according to tumor thickness, anatomic site, and ulceration, and then were prerandomized to either ELND or nodal observation. Femoral, axillary, or modified neck dissections were performed using standardized surgical guidelines. RESULTS: The median follow-up was 7.4 years. A multifactorial (Cox regression) analysis showed that the following factors independently influenced survival: tumor ulceration, trunk site, tumor thickness, and patient age. Surgical treatment results were first compared based on randomized intent. Overall 5-year survival was not significantly different for patients who received ELND or nodal observation. However, the 552 patients 60 years of age or younger (75% of total group) with ELND has a significantly better 5-year survival. Among these patients, 5-year survival was better with ELND versus nodal observation for the 335 patients with tumors 1 to 2 mm thick, the 403 patients without tumor ulceration, and the 284 patients with tumors 1 to 2 mm thick and no ulceration. In contrast, patients older than 60 years of age who had ELND actually had a lower survival trend than those who had nodal observation. When survival rates were compared based on treatment actually received (i.e., including crossover patients), the patients with significantly improved 5-year survival rates after ELND included those with tumors 1 to 2 mm thick, those without tumor ulceration, and those 60 years of age or younger with tumors 1 to 2 mm thick or without ulceration. CONCLUSION: This is the first randomized study to prove the value of surgical treatment for clinically occult regional metastases. Patients 60 years or age or younger with intermediate-thickness melanomas, especially with nonulcerative melanoma and those with tumors 1 to 2 mm thick, may benefit from ELND. However, because some patients still are developing distant disease, these results should be considered an interim analysis.     

Characteristics and clinical outcome of proximal-third gastric cancer

BACKGROUND: It is generally accepted that the prognosis of patients with proximal gastric cancer (PGC) is worse than that of patients with more distal gastric cancer. STUDY DESIGN: The aim of this study was to compare the clinical features and outcomes of PGC with those of middle- and distal-third gastric cancers. A total of 646 primary gastric cancers was analyzed as a retrospective study. RESULTS: Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed, and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate for patients with PGC was significantly lower than that of patients with more distal tumors. When the PGC group was divided into patients with esophageal invasion and without esophageal invasion, patients with esophageal invasion had significantly worse outcomes. When corrected for depth of invasion, lesions with esophageal invasion had significantly worse outcomes than those of other sites in T2 curative cancers. Proximal gastric cancer with esophageal invasion was characterized by a larger tumor, deeper penetration, and a higher incidence of lymph node metastasis compared with tumors in other sites, and in multivariate analysis of all curative cases, these variables were independent prognostic factors for survival. The frequency of positive proximal margins of PGC was higher than those of other sites. CONCLUSIONS: The relatively poor prognosis associated with PGC is mainly from advanced tumor stages of esophageal invasion. Early detection is the most important strategy to improve the survival of patients with PGC. In addition, aggressive lymph node dissection and chemotherapy for esophageal invasion should be considered even if the tumor invasion is moderate (T2 tumor), and a tumor-free margin is important.     

Colour duplex ultrasonography in the rational management of chronic venous leg ulcers

Colour duplex ultrasonographic imaging has largely replaced venography in the assessment of lower-limb venous disorders. This is a study of the use of duplex in the management of patients with chronic venous ulceration in community ulcer clinics. Patients with chronic leg ulceration and an ankle: brachial pressure index of 0.85 or greater were studied. Assessment of venous competence in both the deep and superficial systems of the affected and unaffected legs was performed using colour venous duplex imaging. Reflux was defined as reverse flow for greater than 1 s after manual calf compression. One hundred consecutive patients were assessed over 15 months. Of 111 ulcerated legs, 96 had active ulceration, while 15 had been ulcerated within the previous 6 months. Fifty-seven (51 per cent) of the 111 ulcerated legs had superficial incompetence alone (88 per cent long saphenous system or its perforators, 12 per cent short saphenous system). Six legs (5 per cent) had isolated deep venous incompetence. Forty-two legs had mixed superficial and deep venous reflux; 22 of these had undergone previous venous surgery. Colour venous duplex assessment demonstrated superficial venous disease in approximately half of limbs with chronic leg ulceration. Venous dysfunction in these patients is potentially curable by surgery.     

Tape stripping induces marked epidermal proliferation and altered TGF-alpha expression in non-lesional psoriatic skin

PURPOSE: This study was performed to establish the classification and the treatment modality for recurrent cervical cancer of the vaginal stump after hysterectomy. PATIENTS AND METHODS: Ninety patients with centrally recurrent cervical cancer of the vaginal stump following hysterectomy were treated with high-dose-rate intracavitary brachytherapy with or without external irradiation. The intervals between primary surgery and vaginal recurrences varied from 3 months to 36 years. Tumor size of the vaginal stump was determined by bimanual rectovaginal examination at the time of recurrence and was classified into three groups, i.e., small (no palpable tumor), medium (less than 3 cm), and large (3 cm or more). RESULTS: The 10-year survival rates for all patients were 52%. Survival was greatly influenced by the tumor sizes of the vaginal stump. The 10-year survival rates of patients with small, medium, and large size tumors were 72, 48, and 0%, respectively. All patients with large size tumors died within 5 years. Of 90 patients, 75 (83%) were determined by physical examination to be free of tumor on at least one visit within 2 months of the completion of treatment (CR). The remaining 15 patients (17%) had physical findings suggestive of residual tumor (Residual). The overall 10-year survival rate for all patients with CR was 63%, compared with 10% for the patients with Residual (P < 0.0001). The incidences of distant metastases of the patients with or without local failure were 55 and 13%, respectively (P < 0.0001). The patients with local failure had significantly higher incidence of metastases. Most patients with small size tumor were treated with brachytherapy alone, and the survival rates of these patients were not improved by combination with external irradiation. CONCLUSION: These results suggest that tumor size was a significant prognostic factor for recurrent cervical cancer of the vaginal stump. Patients with small size tumors were recommended to be treated with brachytherapy alone.     

Character of the invasive margin in colorectal cancer: does it improve prognostic information of Dukes staging?

PURPOSE: The clinical significance and prognostic value of the histopathologic parameters used in both the Dukes and Jass classifications were evaluated to select those with an independent effect on survival after radical surgery for colorectal cancer. METHODS: The depth of local spread (limited to the bowel wall or extended beyond it), the number of metastatic lymph nodes (none, 1-4, more than 4), the character of the invasive margin (pushing or infiltrating), and the presence or absence of conspicuous peritumoral lymphocytic infiltration were assessed in 235 patients who had undergone radical resection for colorectal cancer. The influence of these variables on survival was studied by univariate and multivariate analysis. RESULTS: No significant difference in survival was found between patients with conspicuous peritumoral infiltrate and those without it; moreover, multivariate analysis failed to show any independent prognostic value for either lymphocytic infiltration or depth of local invasion. However, the character of the invasive margin and the number of metastatic lymph nodes were identified as the only variables with any independent importance on survival. Based on these data, a new prognostic model may be proposed; it uses the character of the infiltrative margin as a discriminating factor among patients within the lymph node-negative (Dukes A and B stages) and lymph node-positive (Dukes C1 and C2 subsets) groups. A good prognosis for Dukes A, B, and C1 patients was associated with pushing tumors; C1 and C2 patients with infiltrating tumors had a poor prognosis. On the whole, the new prognostic model has allowed for the placement of 59.6 percent of our patients into groups that provide a confident prognosis. The clinical outcome of Dukes A and B patients with infiltrating tumors is still uncertain. CONCLUSIONS: The character of the invasive margin is an important prognostic factor in colorectal cancer. The association of this parameter with the traditional Dukes classification may provide additional useful prognostic information and aid in the selection of those patients who could most benefit from adjuvant therapy.     

Liposarcoma: a population-based epidemiologic and prognostic study of features of 43 patients, including tumor DNA content

Different conceptions exist regarding the epidemiology and prognosis of liposarcoma, and several classification systems are in use. We analyzed a population-based, 25-year series of 43 patients with liposarcoma of the extremity or trunk wall. Follow-up was complete. The annual incidence was 0.12/10(5). The thigh was the most common location. One of 6 tumors was subcutaneous. Deep-seated tumors were larger than s.c. tumors. Among the 42 surgically treated patients, grade II (4-grade scale) was the most common malignancy grade. Four tumors were well-differentiated, 24 were predominantly myxoid, 4 predominantly round-cell, and 10 were predominantly of pleomorphic type. The 5-year metastasis-free survival rate was 69%. By univariate analysis increasing malignancy grade, tumor necrosis, vascular invasion, mitotic count, subtype other than well-differentiated, and high cellularity were prognostic for metastatic disease. However, in the multivariate analysis only tumor necrosis was an independent risk factor. Tumor necrosis should be considered when prognosis of liposarcoma of the extremity and trunk wall is evaluated.     

Osteosarcoma of the pelvis. Oncologic results of 40 patients

The cases of 40 patients with osteosarcoma of the pelvis treated between 1977 and 1994 were reviewed. The location of the tumor was ilium in 30 patients, ischium in four, pubis in one, and sacrum in five. Most (58%) of the tumors were of the chondroblastic subtype. Thirty patients had surgical excision of the tumors: 10 with hemipelvectomies and 20 with limb sparing procedures. A wide margin was achieved in 16 of 30 (53%) patients, including 12 of 14 who had no sacral tumor involvement. Positive margins occurred at the sacrum in 11 patients, lumbar vertebra in one, perirectal space in one, and contralateral pubic body in one. Macroscopic tumor emboli within the regional large vessels were found in seven patients. The incidence of local recurrence was 32%: 13% in wide excisions, 38% in marginal excisions, and 80% in intralesional excisions. The 1- and 5-year overall patient survivals were 73% and 34%, respectively. Patients who had a surgical excision of the primary tumor had a significantly better survival than did those treated without surgery (5-year survival; 41% and 10%, respectively). Tumor size, surgical excision of the primary tumor, surgical margin, and type of surgical procedure were the prognostic factors for patients with Stage IIB tumors.     

Primary small cell carcinoma of the esophagus: a review of the literature with emphasis on therapy and prognosis

BACKGROUND: Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. METHODS: The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. RESULTS: The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P < 0.0001). The median survival was 8 months for patients with LS and 3 months for those with ES. Univariate analysis of LS showed 3 significant prognostic factors: age (for patients age < or =60 years, the median survival was 11 months, whereas for those age >60 years, the median survival was 6 months), tumor size (for those with tumors < or =5 cm, the median survival was 12 months, whereas for those with tumors >5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. CONCLUSIONS: Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors.     

Malignant tracheoesophageal fistula in patients with esophageal cancer

BACKGROUND: Patients with esophageal cancer and a malignant tracheoesophageal fistula (TEF) have an extremely poor prognosis. Additionally, these patients often are denied treatment with radiation therapy because there is concern that these treatments may increase the size and associated problems of the TEF. METHODS: To determine the appropriate treatment (use of radiation therapy) for patients with esophageal cancer and malignant TEF, a review was performed of all such cases seen at the Mayo Clinic between 1971 and 1991. RESULTS: Between 1971 and 1991, 41 patients with malignant TEF arising as a result of esophageal cancer were seen at the Mayo Clinic in Rochester. Twenty-eight of these cancers were locally recurrent, and this group of patients had a uniformly poor outcome (median survival time, 1.4 months). Thirteen patients had a malignant TEF and had not received previous treatment for their esophageal cancer. The median survival length was 4 months for this group of patients. Of the 41 patients in this study, 10 received radiation therapy for their malignant TEF (30-66 Gy). The median survival length of this group of patients was 4.8 months. Six of these 10 patients died of metastatic disease (median survival length, 9 months), and there was no evidence of progression of the local tumor. Four of these 10 patients died of local progression of the malignancy (median survival length, 3 months). CONCLUSIONS: Radiation therapy did not increase the severity of the TEF. The authors conclude that radiation therapy can be administered safely in patients with TEF resulting from esophageal cancer. In some patients, radiation treatment may contribute to stabilization of the local tumor process (60% of patients treated with radiation therapy died of metastatic disease without local progression of tumor); however, all patients in this study eventually died of esophageal cancer.     

Statistical analysis of oropharyngeal squamous cell carcinoma--multivariate analysis of prognostic factors and evaluation of therapeutic modalities]

Ninety-one cases of oropharyngeal squamous cell carcinoma initially treated at Keio University Hospital between July 1981 and June 1996 were reviewed retrospectively. There were 83 males and 8 females, aged from 29 to 83 years old, with an average age of 62.7. The primary lesion was located in the lateral wall in 52 patients (57.1%), the superior wall in 23 (25.3%), the anterior wall in 14 (15.4%) and the posterior wall in 2 (2.2%). Double cancer was detected in 21 patients (23.1%). The patients were divided into two groups according to the initial main treatment of the primary lesion without regard to chemotherapy: 72 patients (79.1%) who received curative radiotherapy with or without salvage surgery, and 14 patients (15.4%) who underwent curative surgery with or without preoperative and/or postoperative radiation. The remaining 5 patients were treated by chemotherapy alone. Prior to the above treatments 50 patients (54.9%) received neoadjuvant chemotherapy (NAC). Survival distributions were estimated by the Kaplan-Meier method as univariate analysis, and compared by the generalized Wilcoxon test. The overall five-year cumulative survival rate was 55.6%. The five-year survival rates according to stage (UICC classification, 1987) were as follows: stage I (11 cases), 70.7%; stage II (12 cases), 63. 6%; stage III (30 cases), 52.3%; and stage IV (38 cases), 52.5%. Significant clinicopathological variables that influenced survival were: (1) T stage (p = 0.0075); (2) age (p = 0.0274); and (3) location of primary lesion (p = 0.0400). The results of multivariate analysis by Cox's proportional hazards model identified T stage as a significant independent prognostic factor. Evaluation of the therapeutic modalities led to the following conclusions. (1) Differences in the initial treatments of the primary lesion were not reflected in the outcome. (2) Salvage surgery for residual or recurrent tumor contributed to improving the survival. The superior wall type, in particular, seemed to be a good indication for salvage surgery. (3) Although the limitations of radiotherapy are not defined clearly, we have to determine the indications for radical resection of tumors resistant to radiotherapy with reconstruction. (4) The response rate of NAC reached 85.4%, but there were no significant differences in survival between the group that underwent NAC and the other group in any other subset analyses. (5) Among the patients who underwent NAC, the responder (CR + PR) group showed a better five-year survival rate (61.3%) than the non-responder (NC + PD) group (42.9%), but the difference was not significant.     

p53 gene alternation in squamous cell carcinoma of the esophagus detected by PCR-cold SSCP analysis

Mutations of the p53 tumor suppressor gene play an important role in the development of common human malignancies. Previous reports revealed that the frequencies of p53 alternations in esophageal carcinoma varied from 26% to 87%. The clinical significance of p53 alternations is still disputed. In the present study, we used polymerase chain reaction--"cold" single-strand conformation polymorphism (PCR-"cold" SSCP)--to investigate p53 genetic alternations in 63 surgical specimens of esophageal squamous cell carcinoma (ESC). Our experiments showed that the optimum buffer temperature for "cold" SSCP analysis was 14 degrees C while the PCR products were around 200-300 bp in size. Among 63 tumorous samples, p53 alternations was detected in 47 tumors, or an incidence rate of 74.6%. For nontumorous mucosal samples, the incidence of p53 alternations was 55.5% (35/63 samples). Additionally, p53 alternations occurred most frequently at exon 6 (50.8%), followed by exon 7 (33.3%), exon 8 (17.5%) and exon 5 (12.7%). Multiple genetic alternations (> or = 2 exons) between p53 exons 5-8 in the same examined samples were found in 21 (33.3%) of 63 tumors, and in 8 (12.7%) of 63 nontumorous mucosal specimens. Our results further showed that p53 alternations did not correlate with age, depth of tumor invasion, lymph node metastasis, tumor stage, cell differentiation or lymphovascular invasion in ESC (P > 0.05). Moreover, the survival rate in patients with p53 alternations was similar to that in patients without p53 alternations (P > 0.05). In conclusion, PCR-"cold" SSCP is a rapid and sensitive method for identifying p53 genetic alternations. p53 genetic alternations occur with a relatively high incidence for ESC, but p53 abnormality has no impact on prognosis.     

Chronologic changes in the clinicopathologic findings and survival of gastric cancer patients

PURPOSE: To determine the chronologic changes in the clinicopathologic features of gastric cancer patients. PATIENTS AND METHODS: The clinicopathologic findings of 1,795 patients with gastric cancer were examined retrospectively from hospital records obtained between 1969 and 1995. The patients were divided into three generations on the basis of chronologic order. The first generation included patients treated over the period 1969 to 1977; the second generation, 1978 to 1986; and the third generation, 1987 to 1995. RESULTS: The chronologic changes in the clinicopathologic findings for all gastric cancers included increases in the superficial type based on macroscopic appearance (P < .005), small-sized tumor (P < .025), superficial depth of invasion (P < .005), and earlier histologic stages (P < .005), in addition to a decrease in lymph node metastasis (P < .005). Overall, the postoperative survival rate has improved over time in gastric cancer patients, with 5-year survival rates of 36.0%, 53.3%, and 68.6% in the first, second, and third generations, respectively. In stages 1,2, and 3, the survival rate in the third generation was the highest of the three generations, whereas in stage 4, the survival rate did not differ between the three generations. Patients who underwent a D2 dissection showed a higher survival rate than those with D1 or D3 dissections, but there was no statistical difference in the survival of patients with D1, D2, and D3 dissections when stage 4 patients were excluded. CONCLUSION: The chronologic changes in gastric cancer patients over the past 27 years have included an increase in the incidence of earlier-staged gastric cancers, which has had a significant impact on the improved postoperative survival rate.     

Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities

We reviewed the cases of sixty-two patients who had had a subcutaneous sarcoma to determine the effect of tumor and treatment-related variables on the rates of survival and local recurrence. Fifty-nine (95 per cent) of the patients had had an operation at another hospital before being referred to us. Twenty-nine (47 per cent) of the sixty-two tumors were high-grade, forty-two (68 per cent) were small (five centimeters or less), and thirty (48 per cent) were malignant fibrous histiocytomas. We followed a treatment strategy that consisted of repeat excision with the goal of obtaining wide margins. Excluding thirteen patients who had had a palpable local recurrence at the time of presentation, twenty (49 per cent) of forty-one patients who had had a marginal excision at another hospital had microscopic residual tumor on repeat excision. At a median of fifty-six months after the repeat excision, fifty (81 per cent) of the sixty-two patients had been continuously disease-free, one had no evidence of disease, eight had died of the disease, and three had died of other causes. The five-year rate of disease-free survival was 85 per cent (fifty-three of sixty-two patients). There were three local recurrences, all in patients who had had a marginal resection. No recurrences were noted in patients who had had a wide local excision of the tumor or of the previous operative field. Multivariate analysis revealed that a large tumor (greater than five centimeters), a marginal excision, and adjuvant radiation therapy were associated with a worse prognosis. Excellent rates of survival for patients who have a subcutaneous sarcoma, including those who have a large or high-grade tumor and those who have residual tumor following a previous operation, can be obtained with carefully planned operative treatment alone. We recommend operative excision or repeat excision with wide margins because of the high prevalence of residual tumor. Size is the most important tumor-related factor, and the operative margin is the most important treatment-related factor. The additional value of adjuvant radiation therapy remains unproved.     

Metastatic esophageal tumors from distant primary lesions: report of three esophagectomies and study of 1835 autopsy cases

Three cases of esophagectomy for secondary esophageal carcinoma metastasized from the ovary, breast and lung are reported. Long-term survival, 14 and 4 years, after esophagectomy was achieved in two patients. The intervals between surgery for primary cancer and dysphagia onset in these two patients were 16 and 7 years, respectively. An aggressive surgical approach appears to be the therapeutic procedure of choice for metastatic esophageal carcinoma when the primary tumor growth rate is suspected to be slow. Autopsy data on 1835 cases revealed 112 (6.1%) had metastasis to the esophagus. The lung was the most common primary tumor-bearing organ and the diffusely infiltrative type was the most common esophageal tumor observed macroscopically which corresponded to the findings in our three patients. When an esophageal stricture with normal mucosa is encountered, a metastatic tumor must be taken into consideration.     

Hepatocellular carcinoma with portal vein tumor thrombus: embolization of arterioportal shunts

PURPOSE: To evaluate transcatheter arterial embolization in patients with hepatocellular carcinoma, portal vein tumor thrombus, and arterioportal shunts. MATERIALS AND METHODS: Ten patients with hepatocellular carcinoma, portal vein tumor thrombus, and severe arterioportal shunting were identified; in these patients, portal blood flow before embolization was hepatofugal. Embolization of arterioportal shunts was performed with steel coils that were introduced through a catheter during arteriography. After embolization, changes in portal hemodynamics and clinical signs and performance status of patients were evaluated; survival rates of patients with and patients without severe arterioportal shunting were compared. RESULTS: In all patients after embolization, angiography showed resolution of arterioportal shunting, and portography showed hepatopetal blood flow in the portal vein trunk. After embolization, performance status of five patients with initial scores of 2 or 3 improved. Ascites resolved in four patients and improved in four patients. One patient died of hepatic failure caused by rupture of esophageal varices 7 days after embolization. Median survival was 4.3 months, and the 6-month and 1-year survival rates were 45% and 12%, respectively. There were no significant differences between survival rates in patients with and patients without severe arterioportal shunting. CONCLUSION: Transcatheter arterial embolization of arterioportal shunts is a useful treatment for improving quality of life in patients with hepatocellular carcinoma.     

Application of the new classification for cancer of the cardia

BACKGROUND: Cancer of the cardia is now topographically classified into three types: type I, with the tumor center in the distal esophagus treated with subtotal esophagectomy; type II, arising at the gastroesophageal junction and treated with distal esophagectomy and either proximal or total gastrectomy; and type III, subcardial cancer treated with extended total gastrectomy. Our objective was to review the new classifications and compare the outcomes in patients grouped and treated according to these classifications. METHODS: Seventy-four patients with cancer of the cardia--15 with type I, 30 with type II, and 29 with type III cancer--underwent surgical resection at our institution between 1992 and 1997. Postoperative complications, UICC stages, and survival (Kaplan-Meier) were compared. RESULTS: The majority of patients with type I (73%) or type II (53%) cancer had stage I or II tumors, but only 27% of patients with type III cancer had this tumor stage (P < .05). Overall 30-day mortality was 4% and morbidity was 31%. Curative resections were performed in 73% (54 of 74) of the patients with 3-year survival rates of 72% (type I), 68% (type II), and 61% (type III). CONCLUSION: The recommended therapy for the different types of cancer of the cardia results in acceptable morbidity, mortality, and survival rates.     

Multinomial-sampling models for random genetic drift

OBJECTIVE: The aim of this study was to determine the usefulness of endosonography for evaluating the effect of neoadjuvant therapy for advanced esophageal carcinoma. MATERIALS AND METHODS: Thirty-four patients with esophageal carcinoma (stage II, 16 patients; stage III, 18 patients) underwent various preoperative treatment. In all patients, endosonography was performed before and after treatment, and the percentage reduction in tumor size was calculated from the maximum area of the tumor. In the 27 patients who underwent surgery, the percentage reduction was compared with the pathologic response. Also, the overall survival rates were compared with the percentage reduction in tumor area. RESULTS: Reduction in tumor area ranged from 0% to 47%. The patients were divided into three groups according to the percentage reduction in tumor area. Pathologic response was graded according to the number of viable cells in the entire lesion. Correlation between pathologic response and percentage reduction in tumor area was strong. We found a significant difference in survival rates among the three groups. CONCLUSION: The percentage reduction in tumor area estimated by means of endosonography reflects the histologic effectiveness of neoadjuvant therapy in patients with advanced esophageal carcinoma and may enable clinicians to predict the prognosis of the disease.     

A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (>/=4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors.     

Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer

BACKGROUND: Current methods of disease staging often fail to detect small numbers of tumor cells in lymph nodes. Metastatic relapse may arise from these few cells. METHODS: We studied 1308 lymph nodes from 68 patients with esophageal cancer without overt metastases who had undergone radical en bloc esophagectomy. A total of 399 lymph nodes obtained from 68 patients were found to be free of tumor by routine histopathological analysis and were studied further for isolated tumor cells by immunohistochemical analysis with the monoclonal anti-epithelial-cell antibody Ber-EP4. This antibody did not stain lymph nodes from 24 control patients without carcinoma. RESULTS: Of the 399 "tumor free" lymph nodes, 67 (17 percent), obtained from 42 of the 68 patients, contained Ber-EP4-positive tumor cells. Fifteen of 30 patients who were considered free of lymph-node metastases by histopathological analysis had such cells in their lymph nodes, and 5 of the 15 had small primary tumors. Ber-EP4-positive cells found in "tumor free" nodes were independently predictive of significantly reduced relapse-free survival (P=0.008) and overall survival (P=0.03). They predicted relapse both in patients without nodal metastases (P=0.01) and in those with regional lymph-node involvement (P=0.007). All 12 patients whose lymph nodes were negative on both histopathological and immunohistochemical analysis and who were available for follow-up survived without recurrence. The presence of micrometastatic tumor cells in bone marrow had no additional prognostic value. CONCLUSIONS: Immunohistochemical examination of lymph nodes may improve the pathological staging of esophageal cancer.     

Endoscopic ultrasonography in the local staging of primary gastric lymphoma

Endoscopic ultrasonography (EUS) and endoscopy were prospectively performed and compared to the histopathologic findings of the resection specimens in 24 patients with primary gastric lymphoma (PGL). On EUS, three types of PGL could be differentiated, a superficial type (n = 10), an infiltrating type (n = 12) and a tumorous type (n = 2). In the correct assessment of surface extension of the tumors, endoscopy and EUS agreed in 37.5% of cases and EUS showed more extensive disease than endoscopy in 58% of cases. However, in comparison to the resection specimens, EUS still underestimated the tumor surface extension in 37.5% of cases; this was mainly in low grade malignant PGL. The depth of tumor infiltration was correctly determined on EUS compared to the resection specimens in 91.5% of cases. Sensitivity, specificity and accuracy of diagnosing lymph node metastases were 100%, 80% and 83%, respectively. We conclude that EUS is a useful pre-therapeutic staging tool for primary gastric lymphoma but there remain some problems in determining the longitudinal and circular tumor spread in order to accurately guide the extent of gastric resection.