Non-curative Group Research Articles

Correlation of Clinicopathological Features and Expression of Molecular Markers With Prognosis After 131I Treatment of Differentiated Thyroid Carcinoma

The aim of this study was to identify molecular markers associated with differentiated thyroid carcinoma (DTC) patients and to determine whether there was a correlation between clinicopathological features or molecular markers and the outcome of radioiodine therapy. We retrospectively reviewed the records of 68 patients with papillary thyroid carcinoma (PTC) and 6 patients with follicular thyroid carcinoma (FTC), who underwent iodine treatment. All patients were divided into a cured group (no evidence for disease) and a noncured group (presence of residual or recurrent disease). Immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER)-2 (C-erbB-2), ephrin receptor (EphA-2), and sodium-iodide symporter (NIS) was performed in all DTC specimens (68 PTCs, 6 FTCs) and in 14 follicular adenoma specimens. Male patients and patients with lymph node and distant metastases had poorer prognosis. Overexpression of ER, PR, HER-2, EphA-2, and NIS was observed in 50.0% (37), 73.0% (54), 52.7% (39), 67.5% (50), and 70.3% (52) of DTC patients, respectively, and was significantly higher than in follicular adenoma patients (0%, 7.14%, 14.29%, 35.7%, and 35.7%, respectively). However, in patients with DTC, no significant difference in the expression of any marker was seen between the cured group and noncured group. Male gender, and lymph node and distant metastases were found to be poor prognostic factors for patients with DTC. Higher expressions of ER, PR, HER-2, EphA-2, and NIS were associated with DTC, but were not correlated with the effectiveness of radioiodine treatment.

The relationship between efficacy of surgical treatment of Cushing disease and pathological – immunohistochemical and ultrastructural – confirmation of corticotroph tumour presence

Background and purposeThe most common cause of Cushing disease (CD) is ACTH-secreting pituitary adenoma. Transsphenoidal selective adenomectomy is the treatment of choice. Frequency of remission varies from 60% to 90%, depending on the site and the surgeon's experience. This study aims to answer the question whether confirmation of corticotroph adenoma in pathological examinations increases the probability of surgical cure for CD. Material and methodsThe prospective study involved 36 patients with CD operated on with the transsphenoidal approach and followed up for at least 18 months. Following the surgical procedure, the specimen was examined by a pathologist. The study evaluated the significance of positive histological (immunohistochemical and ultrastructural) examination results for achieving surgical cure for CD. ResultsTwenty-three of 36 patients (63.9%) were regarded as being surgically cured of CD. Persistent CD was confirmed in 13 patients (36.1%). Pituitary insufficiency was found in 5 patients (13.9%), whereas 3 patients (8.3%) were diagnosed with diabetes insipidus. A significant difference was demonstrated between the cured and the non-cured group with reference to the results of pathological examination of surgical specimens. Pathomorphological confirmation of corticotroph adenoma was significantly more frequently observed in the cured group in comparison with the non-cured group (p = 0.028). ConclusionsPathological confirmation of corticotroph pituitary adenoma may be regarded as an important predictor of the surgical cure of CD.

Predictive value of preoperative magnetic resonance imaging of the pituitary for surgical cure in cushing’s disease

Cushing's disease (CD) is caused by ACTH-secreting pituitary adenoma. Transsphenoidal surgery (TSS) is the treatment of choice. CD diagnosis must be based on biochemical confirmation of hypercortisolemia and visualization of pituitary tumor on magnetic resonance imaging (MRI). Diagnostic problems are associated with equivocal or even normal MRI. In such situations, some neurosurgical centers perform a diagnostic sellar exploration. The purpose of this study was to evaluate the relationship between the results of preoperative MRI of the pituitary and efficacy of TSS for CD. A prospective study enrolling 36 consecutive patients with biochemically confirmed CD operated on and then followed up for at least 18 months. 23 of 36 patients (63,9%) were cured. Persistent CD was confirmed in 13 patients (36,1%). A difference was demonstrated between both groups with reference to the preoperative MR findings. In the cured group there was a significantly greater number of patients with precisely visualized pituitary microadenoma whereas in the non-cured group there was a significantly greater number of patients with pituitary macroadenoma or equivocal result of MRI (p=0.036). Precise localization of corticotroph microadenoma on the preoperative MRI may be considered as one of predictive factors positively prognosticating cure after TSS for CD.

Long-Term Results of Laparoscopic Burch Colposuspension for Stress Urinary Incontinence in Women

We evaluated the long-term efficacy of laparoscopic Burch colposuspension for stress urinary incontinence (SUI) in women. A total of 68 patients who underwent extraperitoneal laparoscopic Burch colposuspensions with more than a 3-yr follow-up were included. The colposuspension was performed by using two non-absorbable sutures on each side. The patients were considered to be cured of SUI if they had a negative result of cough stress test and there were no reports of urine leakage during physical stress. The mean follow-up period was 52 months (range, 36 to 83 months). The overall subjective cure rate was reported in 49 patients (72%). There was no significant difference between the cured and non-cured group in terms of clinical parameters. The cure rate tended to decline gradually over time and it was more deteriorated significantly after 4 yr of surgery. Based on these results, we recommend that long-term follow-up is needed when evaluating the clinical efficacy of anti-incontinence surgery.

Prognostic role of immunosuppressive acidic protein in patients with esophageal cancer

Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the host's immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 +/- 183 mg/mL vs. 739 +/- 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

Clinical Significance of Large Tenascin‐C Spliced Variant as a Potential Biomarker for Colorectal Cancer

Tenascin-C is an extracellular matrix protein forming various types of spliced variants. Low molecule variants are transiently present, but large spliced variants are predominantly overexpressed in proliferative processes or tumorigenesis in some varieties of cancer. However, the detection of the plasma level of large tenascin-C spliced variant (L-Tn-CSV) in colorectal cancer (CRC) has not been clarified. This study was performed to validate elevated plasma L-Tn-CSV levels as a possible biomarker for CRC. Plasma samples were obtained before resection and from time to time postoperatively and stored at -80 degrees C until assay. Plasma L-Tn-CSV levels were evaluated in patients with primary (n = 162) and with recurrent (n = 20) CRC, including 48 healthy volunteers, measured by ELISA. The average plasma L-Tn-CSV concentrations of patients with primary CRC were 5,260 +/- 3,243.3 pg/ml and of patients with recurrent CRC 4,106 +/- 2,261.1 pg/ml, which were significantly elevated in comparison with those of healthy volunteers (2,364.3 +/- 7,49.6). The sensitivity for detecting CRC using plasma L-Tn-CSV was 56.6%, based on the mean +/- 2 SD of the concentrations of healthy controls (3,863.5), which was significantly higher than CEA (40.1%) and CA19-9 (23.6%). No obvious associations were evident between plasma L-Tn-CSV status and values of CEA and CA19-9 respectively. Statistically significant differences in plasma L-Tn-CSV were observed depending on tumor depth, lymph node metastasis, and TNM stage. Negative conversions of plasma L-Tn-CSV levels 6 months after resection were significantly higher in the completely curative resection group than in the non-curative groups (P < 0.001). The plasma L-Tn-CSV may serve very well as a useful biomarker for tumor staging and postoperative monitoring of preoperatively positive CRC that is independent and exceeds conventional tumor markers.

Clinicopathologic Features and Treatment of Residual Early Cancers After Endoscopic Mucosal Resection of the Stomach

We sometimes encounter residual or recurrent cancers after endoscopic mucosal resection (EMR) for early gastric cancer. The aim of the present study was to clarify the clinicopathologic characteristics of and optimal treatment for the residual cancers after EMR. Seventy-four patients with early gastric cancer were treated with EMR between 1994 and 2004. These patients were divided into 2 groups as follows: the curative group (n=59) and the noncurative group (n=15). The clinicopathologic data were compared between the 2 groups and the outcomes of additional therapy were reviewed. In the noncurative group, the tumors were located significantly frequently on the upper or middle third of the stomach compared with the curative group (P<0.05). The number of fragments in EMR was significantly larger in the noncurative group than in the curative group (P<0.05). Fifteen patients required additional treatment because of the residual cancer. Nine (75%) of 12 patients requiring surgery underwent laparoscopic surgery. Three patients were treated by endoscopic therapy. EMR with a single fragment and with a sufficient margin is useful for the complete resection of early gastric cancer. When residual cancer occurs, laparoscopic gastrectomy may be a good alternative.

ASSOCIATION OF A SEX-RELATED DIFFERENCE OF STRONGYLOIDES STERCORALIS–SPECIFIC IgG4 ANTIBODY TITER WITH THE EFFICACY OF TREATMENT OF STRONGYLOIDIASIS

It is difficult to completely eradicate strongyloidiasis, a human intestinal nematode infection with Strongyloides stercoralis with drugs, especially in males. To find host factors involved in the response to treatment, patients infected with S. stercoralis were examined for S. stercoralis-specific antibody titers and the effect of treatment with albendazole on these titers were determined. The cure rate was slightly but not significantly lower in males than in females (P = 0.108). However, a significantly higher titer of S. stercoralis-specific IgG4 antibody was observed in males than in females (P = 0.0097), and the S. stercoralis-specific IgG4 antibody titer was significantly higher in the male non-cured group than in the cured group (P = 0.035). These results suggest that elevation of the S. stercoralis-specific IgG4 antibody titer is associated with resistance to treatment of S. stercoralis infection, especially in males.

How aggressive should we be in patients with stage IV colorectal cancer?

The prognosis for metastatic colorectal cancer is grave. Whether to perform surgical resection or palliative treatment remains controversial for this advanced disease. In this retrospective study, we collected data from patients with Stage IV colorectal cancer to identify prognostic factors for predicting selection criteria for surgical treatment in patients with metastatic disease. A retrospective chart review was performed for patients treated from 1992 to 1999 from the Koo Foundation Sun Yat-Sen Cancer Center Tumor Registry. Seventy-four patients were identified as having Stage IV disease at the time of diagnosis. Data concerning the patients' demographics, laboratory results, operative procedure, mortality, morbidity, and survival were collected. Independent variables and survival time were analyzed by the independent t-test method. The difference was considered statistically significant at P < 0.05. Overall survival time for the patients with Stage IV colorectal cancer was 16.1 months. Survival in the curative resection group was significantly longer than that in the noncurative group (31.9 vs. 12.7; P < 0.016). The operative mortality and morbidity rates were 5.6 percent (4 of 71) and 21.1 percent (15 of 71), respectively. The two most common complications were leakage at the site of anastomosis and urinary tract infection. Based on these results, we conclude that patients older than 65 years, with metastases at multiple sites, intestinal obstruction, preoperative carcinoembryonic antigen level > or =500 ng/ml, lactate dehydrogenase > or =350 units/liter, hemoglobin <10 mg/dl, or hepatic parenchymal replacement by tumor >25 percent have poor prognosis for surgical intervention. Whether to perform primary tumor resection in patients with asymptomatic Stage IV colorectal cancer remains controversial; however, the more aggressively we perform radical resection and metastasectomy to selected patients, the more survival benefits the patients obtain.

Clinical characteristics and prognosis of patients with hepatoblastoma.

Hepatoblastoma is a rare pediatric malignancy that frequently appears in an advanced unresectable stage. Improved resectability and survival rate have been reported with the help of neoadjuvant chemotherapy. Between January 1987 and June 1995 a series of 20 patients were managed with a diagnosis of hepatoblastoma. The median age at diagnosis was 13 months (2 months to 7 years 10 months) with a male/female ratio of 13:7. Chemotherapy effectively reduced the tumor volume (with statistical significance: p = 0.008) and was able to convert seven of nine initially unresectable tumors (78%) to resectable ones. Altogether, 14 operations were done, 12 radical and 2 palliative, with or without adjuvant chemotherapy. The whole population was followed for a median duration of 33 months; and the median survival for the whole group was 26 months. The curative resection group displayed a 5-year survival rate of 61.1%, but none in the noncurative group survived more than 13 months (p = 0.0001). In the univariate analysis for prognostic factors, large tumor size at diagnosis and the absence of thrombocytopenia were associated with poor survival, but these differences were not statistically significant. Pure fetal histology was not associated with better prognosis. In this new era of neoadjuvant chemotherapy, the optimal management strategy for hepatoblastoma is still debated, with radical surgical resection at the earliest possible time being the final goal. For now an individualized approach appears to be the protocol of choice.

Production of a high level of specific IgG4 antibody associated with resistance to albendazole treatment in HLA-DRB1*0901-positive patients with strongyloidiasis.

Strongyloidiasis, a human intestinal infection with Strongyloides stercoralis, is difficult to treat with drugs. The factors influencing this phenomenon remain unclear. To determine the host factors involved in response to treatment, 46 patients with strongyloidiasis were treated with albendazole, followed-up for 1 year, and separated into two groups: cured and non-cured. Serum levels of specific IgA, IgE, IgG, IgG1, and IgG4 antibodies were estimated using S. stercoralis antigen. Significantly higher titers of IgG4 antibody were observed in the non-cured group than in the cured group (P = 0.016). A total of 88 patients were typed for HLA-DRB1 alleles and analyzed for serum levels of antibody. The S. stercoralis-specific IgG4 antibody titers were significantly higher in the HLA-DRB1*0901-positive group than in the negative group (corrected P = 0.044). These results suggest that HLA-DRB1*0901 is a possible genetic marker for resistance to treatment of S. stercoralis that is associated with elevation of S. stercoralis-specific IgG4 antibody titer.

Prognostic factors in rectal cancer

IT HAS been pointed out that there are two outcomes for a patient with rectal cancer: death due to cancer or cure [ 11. The patient is cured if the entire cancer is contained within the operative specimen. The extent to which adjuvant therapy can alter the outcome of the non-curative group remains to be determined. Prognosis is, therefore, influenced almost exclusively by the extent of spread of the tumour and the ability of the surgeon to achieve total clearance [2]. Of foremost importance in prognostication will be those features that distinguish between complete and incomplete excision. Incomplete excision can be proven by the demonstration of either distant metastases (preferably with histopathological confirmation) or residual disease within the tumour bed. Incomplete excision can be inferred if the histopathologist demonstrates transection of tumour at a surgical margin, the deep (circumferential) margin being the most important [3, 41. Incomplete excision is also likely if the tumour has penetrated through the serosal membrane as demonstrated by the presence of tumour cells on the free peritoneal surface (the serosa extends down as far as the mid-point of the mid rectum anteriorly) [4]. Involvement of the apical lymph node (within 1 cm of the level of vessel ligation at the apex of the vascular pedicle) points to the presence of more proximal lymphatic involvement and hence incomplete clearance of lymphatic spread [S]. The preceding features are the most important pointers of an adverse prognosis and their presence or absence should be clearly documented for all patients undergoing surgery for rectal cancer. However, even when these patients are removed as a poor prognosis group, approximately half the remaining patients will eventually die of rectal cancer. [l]. The best explanation for this observation is the presence of occult hepatic metastases at the time of surgery [6]. Prognostication for the apparently cured group is, therefore, an attempt to distinguish between cancers of low and high metastatic potential. It should come as no surprise that the presence of lymph node metastases is the most important prognostic factor for “curative” rectal cancers [l]. A lymph node infiltrated with cancer serves as proof of the acquisition of a metastatic phenotype. Given that the distinction between lymph node-positive and lymph node-negative rectal cancer is of considerable importance, how much effort should be expended in this exercise? How many lymph nodes should be sampled? How many histological sections should be taken from each node? Should monoclonal antibodies to cytokeratin be used to detect small groups of cancer cells? Should fat clearance procedures be adopted? Should circumscribed nodules of tumour without evidence of residual

Survival of noncuratively resected lung cancer

Out of 858 patients who underwent thoracotomy for primary lung cancer, 279 cases were classified as non-curative on the basis of intraoperative and/or post-operative examinations. The causes for non-curative resection were defined as follows: (I) absolutely non-curative resection, (1) palliative tumor extirpation (palliative), (2) remaining tumor in (a) lymph nodes (Ly rem), (b) chest wall or diaphragm (Ch/Dia rem), or (c) bronchial stump (Bro rem), (3) intrapulmonary metastasis (PM), (4) pleural dissemination or pleuritis carcinomatosa (PI/Diss), (5) metastasis in other organs (Meta); (II) relatively non-curative resection, (1) incomplete resection of lymph nodes (R0–1), (2) group 2b or 3 lymph node metastasis (2b Ly). The 5-year actuarial survival rate of the Bro rem group was 35.6%, being the best among the absolutely non-curative cases, followed by the PM group (33.7%), the PI/Diss group (31.6%) and the Ch/Dia rem group (29.7%). The results of the Ly rem and Meta groups were poor at 5.4% and 0%, respectively. Those of the relatively non-curative group were 24.4% (R0–1 group) and 11.6% (2b Ly group). Non-curative resection is not the treatment of choice, but by analyzing the causes of non-curative resection, we may able to improve the prognosis of advanced cases of lung cancer.

Postresection autopsy findings in patients with cancer of the main hepatic duct junction

Extensive resection of the bile ducts combined with hepatic resection is the procedure of choice for carcinoma of the main hepatic duct junction. Currently this procedure is done without great risk, and increasing long-term survival is now the issue. For this purpose, it is necessary to elucidate the biologic properties of the cancer to take reasonable measures. Autopsy findings of patients who died of recurrence may offer a reliable guide. Autopsy findings were studied in 14 patients: eight who had undergone curative resection and six who had received noncurative resection. Cancer recurred at the liver hilum with invasion into adjacent organs. Peritoneal dissemination and lymph node metastases were infrequent. These were common findings in both curative and noncurative resection groups. Cancer cells in the connective tissue of the hepatoduodenal ligament may play a major role in recurrence.

Evaluation of Surgical Treatment of Patients over 75 years of Age with Lung Cancer

Sixty patients with lung cancer over the age of 75 years were admitted from 1973 to February, 1988, and 33 of them were treated surgically.The operative procedures were lobectomy (22 patients), segmentectomy (five patients), pneumonectomy (one patient), sleeve pneumonectomy (one patient) and partial resection (two patients). Absolute curative resection was done in 13 patients (39. 4%), relative curative resection in two (6. 1%), relative non-curative resection in nine (27. 3%), absolute non-curative resection in seven (21. 2%) and exploratory thoracotomy in two (6. 1%).The three-year survival rate after operation for all 33 patients was 37. 7% (66. 7% for stage I-16 patients and 19. 2% for stage III-14 patients).Seventeen patients are alive; ten had absolute curative resection (58. 8%), one had relative curative resection (5. 9%), four had relative non-curative resection (23. 5%) and two had absolute non-curative resection (11. 8%).Postoperative complication developed in 18 patients (54. 5%). The incidence was 84. 6% in the absolute curative group, 50. 0% in the relative curative group, 33. 3% in the relative non-curative group and 28. 6% in the absolute non-curative group. Patients who had absolute curative resection with mediastinal lymph node dissection had a high incidence of postoperative complications. There was no operative mortality in any of the groups.It is concluded that aggressive surgical treatment should be performed regardless of the age of the patient if radical operation is at all feasible.