Increase In Distant Metastasis Research Articles

Prognostic significance of extranodal extension in patients with pathologic N1 non-small cell lung cancer undergoing complete resection.

The prognostic significance of extranodal extension (ENE) remains unclear in patients with pathologic N1 (pN1) non-small-cell lung cancer (NSCLC) undergoing surgery. We evaluated the prognostic impact of ENE in patients with pN1 NSCLC. From 2004 to 2018, we retrospectively analyzed the data of 862 patients with pN1 NSCLC who underwent lobectomy and more (lobectomy, bilobectomy, pneumonectomy, sleeve lobectomy). According to their resection status and the presence of ENE, patients were classified into R0 without ENE (pure R0) (n=645), R0 with ENE (R0-ENE) (n=130), and incomplete resection (R1/R2) groups (n=87). The primary and secondary endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS), respectively. The prognosis of the R0-ENE group was significantly worse than the pure R0 group for both OS (5-year rate: 51.6% vs. 65.4%, P=0.008) and RFS (44.4% vs. 53.0%, P=0.04). According to the recurrence pattern, a difference of RFS was found only for distant metastasis (55.2% vs. 65.0%, P=0.02). The multivariable Cox analysis revealed that the presence of ENE was a negative prognostic factor in patients who did not undergo adjuvant chemotherapy [hazard ratio (HR) =1.58; 95% confidence interval (CI): 1.06-2.36; P=0.03], but it was not in those with adjuvant chemotherapy (HR =1.20; 95% CI: 0.80-1.81; P=0.38). For patients with pN1 NSCLC, the presence of ENE was a negative prognostic factor for both OS and RFS, regardless of resection status. The negative prognostic effect of ENE was significantly associated with an increase in distant metastasis and was not observed in patients who underwent adjuvant chemotherapy.

Detailed pathologic analysis on the co-occurrence of non-seminomatous germ cell tumor subtypes in matched orchiectomy and retroperitoneal lymph node dissections.

The frequency of co-occurrence between germ cell tumor (GCT) components in non-seminomatous germ cell tumor (NSGCT) orchiectomy specimens and their correlation with histologic findings in subsequent retroperitoneal lymph node dissection (RPLND) specimens have not been well characterized. The objective of the study was to report the first detailed clinicopathologic analysis of NSGCT orchiectomy and RPLND samples to determine the likelihood and agreement of the co-occurrence of GCT components. A total of 118 consecutive patients with NSGCT treated between 1988 and 2012 who underwent both orchiectomy and RPLND at a single academic tertiary care center were analyzed. Statistical analysis of co-occurrence likelihood and agreement of GCT components was performed, both within and between orchiectomy and RPLND specimens. Embryonal carcinoma was the most frequent component present in orchiectomy specimens, and there were multiple significant associations between orchiectomy GCT components; seminoma occurred less frequently with embryonal carcinoma (OR 0.29 [95% confidence interval (CI) 0.11-0.75]; p<0.01), and teratoma more frequently occurred with choriocarcinoma (OR 9.64 [95% CI 1.22-76.12]; p=0.01). Presence of teratoma in the orchiectomy specimen predicted for a fourfold increase in distant metastasis on multivariate analysis (HR 4.92 [1.14-18.9]; p=0.02). The only significant association of co-occurrence in the RPLND specimen was between embryonal carcinoma and teratoma (OR 0.01 [95% CI 0-0.07]; p<0.001), where it was significantly less likely for them to occur together. Our findings are limited by their retrospective nature. The co-occurrence of GCT components within orchiectomy specimens does not appear to be a completely random process. However, there is less agreement and more randomness between the occurrence of the GCT components in matched orchiectomy and RPLND samples. In this report, we look at the co-occurrence of different GCT components within matched orchiectomy and RPLND pathology specimens and show that co-occurrence is not a completely random process.

Skeletal Metastasis of Canine Urothelial Carcinoma: Pathologic and Computed Tomographic Features.

Invasive urothelial (transitional cell) carcinoma (UC) is the most common cancer in the canine urinary tract. Prolonged survival of dogs with UC due to better management of the primary tumor and prevention of urethral obstruction might have contributed to an apparent increase in distant metastasis. Metastasis to bone is particularly concerning because the ensuing pain often leads to euthanasia; however, little is known of the frequency, site, or nature of UC skeletal metastasis. In a retrospective analysis, 17 (9%) of 188 canine UC cases had histologically confirmed skeletal metastasis, mainly to the vertebrae. In a prospective analysis of 21 dogs with UC that underwent total body computed tomography (CT) at euthanasia followed by a standardized pathologic examination, skeletal lesions detected on CT were suspected to be metastatic in 4 dogs and were confirmed as metastatic UC histologically in 3 (14%) dogs. In all 3 cases, skeletal metastasis had been suspected based on history and physical examination; however, 1 dog had additional CT-detected skeletal metastases in a clinically unsuspected location, and 2 dogs had histologically confirmed skeletal metastases that corresponded to nonspecific osseous lesions on CT. These findings suggest that total body CT could be helpful in detecting skeletal metastasis as a cause of bone pain in dogs with UC as well as in identifying clinically "silent" sites of skeletal metastasis.

P-cadherin as prognostic factor for loco-regional relapse in breast cancer.

Breast cancer is the most frequent malignant tumor and the leading cause of cancer death in women in Portugal. Due to its relation to an increase in distant metastasis and subsequent death, loco-regional relapse is one major concern in breast cancer women. Several classic prognostic factors as tumour size, nodal stage, histological grade, HER2 status and hormonal receptors have been identified as the most important factors for determining loco-regional relapse, disease free and overall survival. However, there is heterogeneity in prognosis and tumor behaviour in patients with identical disease staging and a similar pattern of expression of known molecular markers, hence the need to discover new prognostic factors. One of the possibilities is P-cadherin, already described by researchers as a possible independent marker of prognosis in breast cancer. The aim of this work was to study in a retrospective series of patients the correlation of P-cadherin expression with loco-regional recurrence in breast cancer women. We analyzed the clinical records of 1432 consecutive patients with breast cancer and treated in a University Hospital over a 10 year period. Patients with loco-regional relapse (n=101) without prior or simultaneous distant disease were selected as case group. Control group consisted of patients with more than 10 years follow-up and without disease progression. For both groups demographic, clinical, pathological and molecular markers were analyzed. Tissue micro-arrays were constructed to study P-cadherin expression from 86 tumors with available paraffin embedded blocks. Mean time to recurrence was 41 months and mean survival time after recurrence was 33 months, with a 5-year survival rate of 55%. Tumour size, nodal status and histological grade were identified as independent markers of prognosis. P-cadherin was associated with higher histological grades and hormone negative tumours. P-cadherin was identified as an independent prognostic marker for disease free survival, but not for overall survival. P-cadherin was related to other known factors of worse prognosis and had an independent relation to disease-free survival. P-cadherin might constitute a novel therapeutic target, but its real biological value is yet to be determined. Doubt persists whether it is an independent marker of tumour behaviour or only a surrogate marker of a set of clinical and molecular features related with worse prognosis.

Reduction of β-catenin expression in hepatocellular carcinoma inhibited the enhanced metastatic potential of hypoxia

Objective To explore the role of β-catenin in the proinvasive consequences of hypoxia in hepatocellular carcinoma (HCC).Methods We established in vitro and in vivo hypoxic models using the highly metastatic MHCC97 and the stable red fluorescent protein-expressing MHCC97-R cells.The role of β-catenin in hypoxia-mediated aggressiveness was investigated by β-catenin knockdown.Results Hypoxia caused a pronounced arrest of proliferation in MHCC97 cells,suppressed tumor growth in MHCC97-R xenografts,but promoted in vitro invasiveness and in vivo metastasis.β-Catenin-silencing by short hairpin significantly inhibited the enhanced invasiveness of MHCC97 cells due to hypoxia,reduced the increase in distant metastasis by hepatic arterial ligation,but failed to further restrain cell proliferation.Conclusion β-Catenin in HCC cells plays an essential role in the hypoxia-induced metastatic potential.A reduction of βcatenin expression inhibited the proinvasive consequences of hypoxia in HCC. Key words: β-catenin; Hepatocellular carcinoma; Hypoxia; Malignant potential

Preoperative concurrent chemoradiotherapy plus radical surgery for advanced squamous cell carcinoma of the oral cavity: an analysis of long-term results.

Locoregionally advanced squamous cell carcinomas of the head and neck continue to be a major clinical problem. We demonstrated in 1996 that preoperative concurrent cisplatin- or carboplatin-based chemotherapy and radiotherapy plus radical surgery in advanced oral cancer had minimal toxicity, had high clinical tumor response rates, was well tolerated and produced impressive complete response rates and a high 5-year survival rate. The purpose of the present study was the long-term follow-up of this treatment regimen for advanced oral carcinoma. Forty-eight patients with squamous cell carcinoma of the oral cavity (including soft palate) were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy, and 2-6 weeks later underwent curative surgery. All patients with advanced Stage II (n=7), Stage III (n=22) and Stage IV (n=19) were treated and followed for an average of 7.2 years (range: 61-144 months). The overall actuarial survival of all patients was 81.3% at 5 years and also at 10 years. Progression-free survival at both 5 and 10 years was 84.8% for all patients, and 85.7% for Stage II, 90.0% for Stage III, and 78.9% for Stage IV patients. Progression-free survival rates according to the histopathologic regression grade of primary tumor following preoperative chemoradiotherapy at 10 years were 40. 0% for Grade IIa, 88.9% for Grade IIb, 100% for Grade III, and 87.5% for Grade IV. Patients who achieved good responses histopathologically (Grades IIb, III, IV) had superior survival rates in comparison to patients with extensive residual tumor (Grade IIa) in surgically resected specimens (p=0.0012). A better histologic regression grade was also associated with a higher survival rate even in the long-term analysis. This treatment regimen for advanced oral cancer produced high clinical and pathologic complete response and survival rates with an acceptable acute toxicity profile and lack of late therapeutic complications. The long-term follow-up showed gratifying results even for advanced oral cancers without a substantial increase in distant metastasis and second primary malignancy.

Malignant melanoma of cervical and parotid lymph nodes with an unknown primary site

Forty-six patients with malignant melanoma metastatic to cervical or parotid lymph nodes with an unknown primary site were treated at UCLA Medical Center from 1964 through 1991. Treatment consisted of parotidectomy and/or neck dissection with or without adjuvant therapy. The initial presentation was a cervical mass in 74% and a parotid mass in 26% of patients. Metastasis distal to the head and neck nodal basins developed in 22% of patients. Involvement of more than four cervical or parotid nodes resulted in a significant increase in distant metastasis (P < .01). Adjuvant therapy was found to have no significant effect on survival rates. However, age at the time of diagnosis influenced the survival rates. The significance of the improved survival of these patients as compared to those with a known primary melanoma is discussed.

The prognostic significance of soft tissue extension in Ewing's sarcoma.

From January 1969 through December 1977, 28 patients were treated at the University of Florida with the diagnosis of Ewing's sarcoma. All patients received radiation therapy to the primary site and adjuvant chemotherapy according to several different regimens. A retrospective analysis was carried out to determine the prognostic significance of gross extraosseous extension by the primary lesion. Gross soft tissue extension at the primary site was found to be of prognostic importance. Patients with soft tissue extension more often presented with metastatic disease (39 versus 10%). The five-year survival rate for patients presenting without distant metastasis and whose primary lesions were grossly confined to bone was 87% compared to 20% for those with extraosseous extension. The decrease in survival with soft tissue extension resulted from an increase in distant metastasis as well as local failure, and was independent of primary site location. The proportion of patients with extraosseous extension should be reported in subsequent analyses of local control and survival.

Hyperbaric oxygen as a radiotherapeutic adjuvant in advanced cancer of the uterine cervix.Preliminary results of a randomized trial

From September 1968 to March 1974, a randomized clinical trial was carried out, using conventional fractionation, i.e., five treatments per week, in 233 patients with advanced cancers of the uterine cervix--Stages IIB, IIA, IIIB and IVA. The age limit was 70 years and all patients had medical clearance. Lymphangiography and, in some patients, an exploratory laparotomy with selective lymphadenectomy, were done prior to treatment to determine the extent of nodal disease. The staging has not been changed either by lymphangiogram or lymphadenectomy findings. A few patients with bulky Stage I and IIA lesions were entered into the trial because of extensive nodal disease demonstrated either by lymphangiogram and/or lymphadenectomy. First, the patients were grouped according to the clinical stage. The secondary stratification was according to the lymphangiogram and/or selective lymphadenectomy findings. The patients were then randomized to air or hyperbaric oxygen within each group. The patients were pressurized in a Vickers chamber at 3 atmosphere absolute, using a 20-minute soak time prior to the irradition. The size of the external beam portal was determined by the status of the nodes. The difference in absolute NED (no evidence of disease) survival rates for both groups as a whole and by stages is not statistically significant. There is no difference in the incidence of failures in the irradiated area between the HPO and air patients. There is no increase in distant metastases in the HP group. It does not seem that the HPO has had an effect on the major complications. However, there was an increase in the incidence of complications with extended fields. The addition of lymphadenectomy had increased the incidence of fatal complications, even with routine pelvic portals. The negative results of this trial with conventional fractioantion should not lead to the conclusion that HPO could not be useful with schemes using a few high dose fractions.

Postoperative radiation in the treatment of carcinoma of the breast

As a result of a decision to carry out preliminary selective biopsy on patients with operable stage I and II (Manchester) carcinoma of the breast followed by radical mastectomy, accurate knowledge became available of lymphatic metastases to all sites, including internal mammary nodes. Of 121 patients with pathologic stage I disease (those with no evidence of lymphatic metastases), 88 received prophylactic postoperative radiation and 33 were not irradiated. All have been followed up for ten years. Of the irradiated group, fourteen showed evidence of distant recurrence; of these, seven died in the first three years after treatment whereas only three in the nonirradiated group showed distant recurrence and none of them died before the fifth year. Although short of statistical significance, this result suggests that prophylactic radiation directed to areas shown to be free of lymphatic metastases, as would be expected, does no good in the prevention of local recurrence and may do harm by an increase in distant metastases resulting in the earlier death of the patient.

Postoperative radiation in the treatment of carcinoma of the breast

<h2>Abstract</h2> As a result of a decision to carry out preliminary selective biopsy on patients with operable stage I and II (Manchester) carcinoma of the breast followed by radical mastectomy, accurate knowledge became available of lymphatic metastases to all sites, including internal mammary nodes. Of 121 patients with pathologic stage I disease (those with no evidence of lymphatic metastases), 88 received prophylactic postoperative radiation and 33 were not irradiated. All have been followed up for ten years. Of the irradiated group, fourteen showed evidence of distant recurrence; of these, seven died in the first three years after treatment whereas only three in the nonirradiated group showed distant recurrence and none of them died before the fifth year. Although short of statistical significance, this result suggests that prophylactic radiation directed to areas shown to be free of lymphatic metastases, as would be expected, does no good in the prevention of local recurrence and may do harm by an increase in distant metastases resulting in the earlier death of the patient.

Postoperative radiation in the treatment of carcinoma of the breast

As a result of a decision to carry out preliminary selective biopsy on patients with operable stage I and II (Manchester) carcinoma of the breast followed by radical mastectomy, accurate knowledge became available of lymphatic metastases to all sites, including internal mammary nodes. Of 121 patients with pathologic stage I disease (those with no evidence of lymphatic metastases), 88 received prophylactic postoperative radiation and 33 were not irradiated. All have been followed up for ten years. Of the irradiated group, fourteen showed evidence of distant recurrence; of these, seven died in the first three years after treatment whereas only three in the nonirradiated group showed distant recurrence and none of them died before the fifth year. Although short of statistical significance, this result suggests that prophylactic radiation directed to areas shown to be free of lymphatic metastases, as would be expected, does no good in the prevention of local recurrence and may do harm by an increase in distant metastases resulting in the earlier death of the patient.