Showing papers on "Surgical oncology published in 2005"

Expression of the Transcription Factors Snail, Slug, and Twist and Their Clinical Significance in Human Breast Cancer

Abstract: Background Slug, Snail, and Twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin. We examined the distribution and expression of these three molecules together with the methylation of the Twist gene promoter in human breast cancer to elucidate their clinical significance. Methods Frozen sections from breast cancer primary tumors (tumor, n = 114; background, n = 30) were immunostained with Slug, Snail, and Twist antibodies. RNA was reverse-transcribed, quantified, and analyzed by quantitative polymerase chain reaction (Q-PCR). Results were expressed as copy number of transcript per 50 ng of RNA (standardized against β-actin). Results Immunohistochemistry revealed that all three molecules were stained in mammary tissues, with an increase in Twist within tumor tissues; this was supported by Q-PCR analysis. Q-PCR analysis showed that Slug was elevated with increasing tumor grade and prognostic indices. Twist was elevated with increasing nodal involvement (tumor-node-metastasis status). Conversely, Snail was reduced in expression corresponding with prognostic indices and tumor grade. Increased levels of Slug were associated with tumors from patients with metastatic disease or disease recurrence, and increased expression of Twist was associated with tumors from patients who had died from breast cancer. It is interesting to note that Snail expression was significantly reduced in patients with a poor outcome and those who had node-positive tumors. In addition, tumors exhibited methylation of the Twist promoter. Conclusions These data demonstrate that all three transcription factors have inappropriate expression in breast cancer and that this may play a part in the progression of human breast tumors.

Retrorectal tumors: a diagnostic and therapeutic challenge.

Abstract: Tumors occurring in the retrorectal space are heterogeneous and uncommon. The utility of newer imaging techniques has not been extensively described, and operative approach is variable. This study examined the diagnosis, treatment, and outcome of retrorectal tumors at a tertiary referral center. Patients with primary, extramucosal neoplasms occurring in the retrorectal space were identified using a prospectively maintained, procedural database of all adult colorectal surgical patients (1981–2003). Patients also were incorporated from the gynecologic oncology service. Exclusion criteria included inflammatory processes, locally advanced colorectal cancer, and metastatic malignancy. Medical records, radiology, and pathology reports were reviewed retrospectively. Thirty-four patients with retrorectal tumors were treated. Malignant tumors comprised 21 percent. Older age, male gender, and pain were predictive of malignancy (P < 0.05). Sensitivity of proctoscopy was 53 percent; this increased to 100 percent with the use of transrectal ultrasound. Accuracy of magnetic resonance vs. computed tomographic imaging for specific histologic tumor type was 28 vs. 18 percent, respectively. Surgical approach was anterior (n = 14), posterior (n = 11), and combined abdominoperineal (n = 9). Eleven patients required en bloc proctectomy. Patients undergoing posterior resection had lower blood loss and required fewer transfusions (P < 0.05). All benign tumors were resected with normal histologic margins and none recurred (median follow-up, 22 months). All patients with malignancy had recurrence/recrudescence of their disease. For these patients, median disease-free and overall survivals were 38 and 61 months, respectively. Retrorectal tumors remain a diagnostic and therapeutic challenge. Pain, male gender, and advanced age increase the likelihood of malignancy. Various imaging modalities are useful for planning resection but cannot establish a definitive diagnosis. Whereas benign retrorectal tumors can be completely resected, curative resection of malignant retrorectal tumors remains difficult.

Less is (usually) more: when is amputation appropriate for treatment of extremity soft tissue sarcoma?

Abstract: Limb-salvage surgery, combining wide excision and radiotherapy, is the standard of treatment for patients with extremity soft tissue sarcoma. In the only randomized study comparing amputation with limb preservation, Rosenberg et al. demonstrated that despite slightly higher local recurrence rates, limb salvage was not detrimental to patient survival. This is a common finding in solid tumor biology: organ preservation is not associated with worse overall survival, even though patients often have more local recurrences. Indeed, breast-conservation therapy is preferred over mastectomy and has been proven to be as effective in multiple randomized studies. We also see this, for example, in such diverse tumors as laryngeal cancer and anorectal melanoma. This trend of ‘‘less is more’’ in surgery is well founded and leads to improved patient satisfaction and quality of life (QOL) without compromising quantity of life. In this issue of Annals of Surgical Oncology, Ghert et al. 5 from the Princess Margaret Hospital present a series of patients undergoing amputation as the primary surgical procedure for treatment of extremity soft tissue sarcoma. In their prospective database, they found that only 6% of patients (25 of 413) required amputation as initial surgical treatment. This is in keeping with data from other institutions, where the rates of initial amputation have decreased from approximately 40% to approximately 5% as more effective surgical and oncological strategies evolve and as our understanding of the natural history of these malignancies improves. There is still a role for amputation, and in this series there were three major indications: (1) anticipated inadequate limb function after wide excision, (2) multicompartmental neurovascular tumor involvement, and (3) local tumor contamination from unplanned prior surgery. Although local recurrences were not discussed in either patient group, one would expect lower rates of local relapse in those undergoing amputation. Despite this expectation, on univariate analysis, patients undergoing amputation had higher rates of systemic relapse, which on multivariate analysis was accounted for by the larger tumor size in these patients. As alluded to previously, more radical surgery does not seem to improve survival. With this in mind, the limits of limb-sparing surgery are pushed to their maximum. Larger and deeper tumors undergo wide excision and no longer require anatomical compartmental resection unless this is dictated by tumor location. Radiotherapy plays a key role in the local control of the tumor. It too is the subject of vigorous investigation of the optimal timing and dose and the effects on patient outcome and satisfaction. For example, patients treated with postoperative radiation have fewer wound complications than those treated before surgery. Despite improved early functional status in those irradiated after surgery, outcomes ultimately seem equivalent. These issues are not mundane. If we are to offer patients less surgery, anticipating equivalent survival but better QOL outcomes, then we need to be mindful of the alternatives and the consequences of the treatment prescribed for their care. Many surgeons consider amputation if sacrifice of the sciatic nerve is required. However, we have shown, in the Received September 27, 2004; accepted October 18, 2004. Address correspondence and reprint requests to: Gary N. Mann, MD; E-mail: gnmann@u.washington.edu.

Cancer cell adaptation to chemotherapy.

Abstract: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.

Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC® is a predictor for relapse: A preliminary report

Abstract: Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery. 30 patients treated for lung cancer with surgery were monitored for circulating epithelial cells (CEC) by taking peripheral blood samples before, 2 weeks and 5 months after surgery and/or radiotherapy (RT) chemotherapy (CT) or combined RT/CT using magnetic bead enrichment and laser scanning cytometry (MAINTRAC®) for quantification of these cells. In 86% of the patients CEC were detected before surgery and in 100% at 2 weeks and 5 months after surgery. In the control group, which consisted of 100 normal donors without cancer, 97 % were negative for CEC. A significantly higher number of CEC was found preoperatively in patients with squamous cell carcinoma than in those with adenocarcinoma. In correlation to the extent of parenchymal manipulation 2 weeks after surgery, an increase in numbers of CEC was observed with limited resections (18/21) whereas pneumonectomy led to a decrease (5/8) of CEC, 2 weeks after surgery. The third analysis done 5 months after surgery identified 3 groups of patients. In the group of 5 patients who received neo- or adjuvant chemo/radiotherapy there was evidence that monitoring of CEC can evaluate the effects of therapy. Another group of 7 patients who underwent surgery only showed a decrease of CEC and no signs of relapse. A third group of 11 patients who had surgery only, showed an increase of CEC (4 with an initial decrease after surgery and 7 with continuous increase). In the group with a continuous increase during the following 24 months, 2 early relapses in patients with stage Ia adenocarcinoma were observed. The increase of CEC preceded clinical detection by six months. We consider, therefore, that patients with adenocarcinoma and a continuous increase of CEC after complete resection for lung cancer are at an increased risk of early relapse.

Evaluation of Residual Glandular Tissue After Skin-Sparing Mastectomies

Abstract: Background The oncological safety of skin-sparing mastectomy (SSM) has been the object of several studies.

Pathophysiology of seroma in breast cancer.

Abstract: Purpose Seroma is the most common complication of mastectomy. The aim of this systematic review is to clarify the pathophysiology of seroma.

Pathophysiology, diagnosis, and treatment of gastrointestinal stromal tumors

Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Activating mutations of KIT or the platelet-derived growth factor receptor alpha gene (PDGFRA) have been identified in the vast majority of GISTs. The respective oncoproteins exhibit constitutive tyrosine kinase activity and promote cell growth. KIT and PDGFRA mutations are rarely found in GISTs in patients with neurofibromatosis type 1 (NF1) suggesting that the pathogenesis of GIST in NF1 patients is different from that in non-NF1 patients. Endoscopic diagnosis of GIST is usually difficult. Endoscopic ultrasonography (EUS)-guided fine-needle aspiration biopsy (EUS-FNAB) is a useful method for the diagnosis of GIST and for the detection of KIT or PDGFRA mutations. Imatinib mesylate, a tyrosine kinase inhibitor known to inhibit the activities of BCR-ABL, KIT, and PDGFR, is currently being used for the treatment of both chronic myeloid leukemia and metastatic GIST. The clinical response to imatinib therapy correlates with the types of mutations of KIT and PDGFRA, and the determination of KIT and PDGFRA mutations is useful for predicting the effect of imatinib. Resistance to imatinib after an initial response has been reported; secondary point mutations in KIT or PDGFRA that confer imatinib resistance are the most common mechanisms responsible for acquired resistance to imatinib. The continued development of target-specific therapies should increase the probability of cure in most patients with GISTs.

The surgical management of primary tumorsof the spine: initial results of an ongoing prospective cohort study.

Abstract: Study Design. Prospective cohort study. Objectives. To prospectively validate the application of appendicular surgical oncology principles to the treatment of primary bone tumors of the spine at a quaternary care spine center using local recurrence, survival, and health-related quality of life as outcome measures. Summary of Background Data. There is clear evidence that violating the margins of a sarcoma or other malignancy during surgical resection will risk local recurrence and diminish overall survival. Previous publications have retrospectively demonstrated this oncologically sound approach to spine tumor management to be internally valid. The external validity or limited generalizability has not been assessed. Methods. Included were all patients who underwent en bloc surgical resection of a primary tumor of the spine between January 1994 and November 2003, at the authors’ institution. Patients were uniformly staged before surgery and baseline demographic and surgical variables were recorded, as well as a cross-sectional evaluation of generic health-related quality of life. Results. Twenty-six patients (12 males and 14 females) were eligible for the study. Average age was 42 (range 16 to 70). There were 19 malignant tumors and 7 benign. There are 20 surviving patients with an average follow-up of 41.5 months (range 6 to 111 months), 15 of whom had malignant tumors. None of these patients have evidence of local recurrence, and one has evidence of systemic disease. The health-related quality of life, using the SF-36, shows acceptable morbidity of these procedures (physical component summary = 37.73 ± 11.52, MCS = 51.69 ± 9.54). Conclusions. Principles of wide surgical resection, commonly applied in appendicular oncology, can and should be used for the treatment of primary bone tumors of the spine with anticipated acceptable morbidity and satisfactory survival.

Repeat Hepatectomy for Recurrent Colorectal Metastases

Abstract: Purpose To determine the risks and benefits of repeat hepatectomy for hepatic metastases from colorectal cancer.

Optimising surgical management of elderly cancer patients

Abstract: Elderly population is on rise. It is an ethical dilemma how aggressive one should be when it comes to treat cancer in elderly. Presumed fear of increased postoperative morbidity and mortality has resulted in delivery of sub-optimal cancer surgery. In this review article we visit physiology of the aged, tools available to assess surgical risks in oncogeriatric patients, and current practice in the management of common cancers encountered in surgical oncology, with the view of increasing awareness on optimising surgical management of senior patients with cancer. A pubmed search for cancer, surgery, elderly, was carried out. Cancer is on rise with increasing age predominantly affecting breast, gastrointestinal tract and lung. Increasingly more surgeons are offering surgery to elderly cancer patient but selection bias is prevalent. Available data reflect short and long-term outcome of cancer surgery in elderly is not greatly different to that of younger patient. Declining physiological reserve along with inability to respond adequately to physiological stress are salient age related changes. C omprehensive G eriatric A ssessment (CGA) is not tested in surgical patient. There is need for a tool to define individualised operative risk. Preoperative assessment of cancer in elderly is designed to offer this information based on functional status of an individual utilising currently available tools of risk assessment. All elderly cancer patients should be offered optimal treatment depending on their functional status not on chronological age. Oncogeriatric patient would benefit from dedicated multidisciplinary approach. Recruitment of elderly cancer patients to more clinical trials is needed to enhance our knowledge and to offer optimum treatment to this unique subgroup.

Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy

Abstract: Introduction The amounts of estrogen receptor (ER) and progesterone receptor (PgR) in a primary tumor are predictive of the response to endocrine therapies of breast cancer. Several patients with ER-positive primary tumors relapse after adjuvant endocrine therapy with no ER expression in the recurrent tissue; much fewer with a recurrent disease after an ER-negative primary tumor may become endocrine responsive. These sequences of events indicate that a phenotype based on ER expression may not be a permanent feature of breast cancer.

Germ cell tumors of the testis.

Abstract: Testicular cancer is the most common malignancy in men aged 20 to 35 years and accounts for approximately 1% of all male malignancies. Through the appropriate utilization of clinical trials, effective treatment paradigms have been developed for the management of all stages of testicular cancer. The multidisciplinary approach to the management of germ cell tumors of the testis has resulted in survival rates of > 90% overall. This review summarizes the principal management of germ cell tumors of the testis, highlighting the indications for surgery, controversies surrounding the integration of surgery, and alternative management strategies.

Caffeine suppresses metastasis in a transgenic mouse model: a prototype molecule for prophylaxis of metastasis

Abstract: A significant fraction of cancer patients have occult disseminated tumors at the time of primary diagnosis, which usually progress to become clinically relevant lesions. Since the majority of cancer mortality is associated with metastatic disease, the ability to inhibit the growth of the secondary tumors would significantly reduce cancer-related morbidity and mortality. We have investigated whether caffeine, which has been shown to suppress tumor cell invasiveness and experimental metastasis, can suppress metastasis in a spontaneous transgene-induced mammary tumor model. Chronic exposure to caffeine prior to the appearance of palpable mammary tumors significantly reduced both tumor burden and metastatic colonization. However, when caffeine exposure began after the appearance of frank tumors, caffeine suppressed metastasis without changing primary tumor burden. The means by which caffeine suppressed metastatic activity may be associated with inhibition of malignant transformation of mammary epithelial cells, inhibition of conversion of dormant tumor cells to micrometastases, micrometastases to macrometastases, or inhibition of tumor cell adhesion and motility. Gene and protein expression patterns resulting from caffeine treatment showed that metastasis suppression may be associated with up-regulation the mRNA expression of multiple extracellular matrix genes, including Fbln1, Bgn, Sparc, Fbn1, Loxl1, Col1a1, Col3a1, Col5a1, Col5a2, Col5a3, Col6a1, Col6a2, and Col6a3. These data suggested that caffeine or other methyl xanthine derivatives may improve the clinical outcome in patients prior to and following the diagnosis of metastatic disease, and could potentially reduce the morbidity and mortality associated with disseminated tumors.

Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1

Abstract: Cancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets. Paraffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data. VEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1. Angiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

Abstract: Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.

TNFerade, an Adenovector Carrying the Transgene for Human Tumor Necrosis Factor α, for Patients With Advanced Solid Tumors: Surgical Experience and Long-Term Follow-Up

Abstract: Background Over the last several years, attempts have been made to use the tumoricidal effects of tumor necrosis factor (TNF)-α to treat cancer. Many of these studies demonstrated dose-limiting systemic side effects from high concentrations of TNF-α. The recent focus has been on developing a local delivery system for TNF-α to minimize the systemic response.

Randomized phase II – study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer – PARC: study protocol [ISRCTN56652283]

Abstract: Background Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR.

Non-small-cell lung cancer: reirradiation for loco-regional relapse previously treated with radiation therapy.

Abstract: Background We evaluated the efficacy and toxicity of reirradiation for patients with loco-regional relapse of non-small-cell lung cancer after radiation therapy.

The impact of bilateral breast cancer on the prognosis of breast cancer: a comparative study with unilateral breast cancer.

Abstract: Background The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We assessed the impact of synchronous and metachronous bilateral breast cancer on the prognosis compared with unilateral breast cancer.

Primary gastric choriocarcinoma: two case reports and a pooled analysis of 53 cases

Abstract: Primary gastric choriocarcinoma (PGC) is a rare tumor. In total, approximately 140 cases of PGC have been reported in the international medical literature. However, the clinical behavior, tumor characteristics, and prognostic parameters of PGC have not been clearly described. We conducted a pooled analysis to clarify the tumor characteristics and prognostic parameters in 53 patients with PGCs, including 2 patients treated at our hospital. The following variables were examined as potential prognostic factors: (1) sex, (2) age, (3) depth of invasion, (4) size, (5) histology, (6) nodal metastasis, (7) distant lymph node metastasis, (8) synchronous liver metastasis, (9) residual tumor, and (10) chemotherapy (not given or given). Univariate and multivariate analyses showed that the presence of residual tumor and synchronous liver metastasis and the absence of chemotherapy were significantly associated with an increased hazard rate (HR) of short overall survival (OS). Pooled analysis, including the two patients with PGC treated at our facility, demonstrated that the presence of a curative operation and chemotherapy, and the absence of synchronous liver metastasis were the strongest indicators of a favorable clinical course in patients with PGC.

Surgical management of skin cancers: experience from a regional cancer centre in North India.

Abstract: AIMS: To review the disease profile and treatment outcome of patients with primary skin malignancies treated at a regional cancer centre. SETTINGS AND DESIGN: Surgical oncology unit of a tertiary care regional cancer centre. Evaluation of treatment outcome of patients with skin cancer from Surgical Oncology database was done. MATERIALS AND METHODS: Retrospective analysis of records of 77 patients with skin cancers treated between 1995 and 2002 was conducted. Profile of patients with skin cancer, surgical details including the management of primary tumour, regional lymph nodes and reconstructive procedures performed and survivals were analysed. STATISTICAL ANALYSIS: All computations were done using the Statistical Package for Social Sciences (SPSS-9). Descriptive statistics were calculated in a standard fashion and survival analysis was performed using Kaplan-Meier method. RESULTS: Skin cancers constituted 2.4% (77/3154) of patients with cancer treated in the surgical oncology department. Squamous cell carcinoma (SCC) was the most common histological type (55.8%) followed by melanoma (26.1%) and basal cell carcinoma (BCC, 18.1%). Forty one percent of patients had undergone some form of intervention elsewhere before being referred. Reconstruction was required in 55.8% patients with large postresection defects. Regional lymph nodal dissection was required in 32.4% of total patients. Five-year median disease-free survival for the entire study population was 75%. CONCLUSIONS: Skin cancers constitute a small but significant proportion of patients with cancer. Unlike in the Western countries, SCC is the commonest histologic variety. Primary level inadequate intervention is very common. Optimal results can be obtained with radical surgery and optimal surgical margins along with a reconstructive procedure when needed.

The estrogen receptor-α A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: results from a population-based study

Abstract: Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor-α (ER-α), occur during breast cancer development. A point mutation in ER-α (nucleotide A908G), producing an amino acid change from lysine to arginine at codon 303 (K303R) results in receptor hypersensitivity to estrogen. This mutation was initially reported in one-third of hyperplastic benign breast lesions, although several recent studies failed to detect it in benign or malignant breast tissues. We screened 653 microdissected, newly diagnosed invasive breast tumors from patients in the Carolina Breast Cancer Study, a population-based case-control study of breast cancer in African American and white women in North Carolina, for the presence of the ER-α A908G mutation by using single-strand conformational polymorphism (SSCP) analysis and 33P-cycle sequencing. We detected the ER-α A908G mutation in 37 of 653 (5.7%) breast tumors. The absence of this mutation in germline DNA confirmed it to be somatic. Three tumors exhibited only the mutant G base at nucleotide 908 on sequencing, indicating that the wild-type ER-α allele had been lost. The ER-α A908G mutation was found more frequently in higher-grade breast tumors (odds ratio (OR) 2.83; 95% confidence interval (CI) 1.09 to 7.34, grade II compared with grade I), and in mixed lobular/ductal tumors (OR 2.10; 95% CI 0.86 to 5.12) compared with ductal carcinomas, although the latter finding was not statistically significant. This population-based study, the largest so far to screen for the ER-α A908G mutation in breast cancer, confirms the presence of the mutant in invasive breast tumors. The mutation was associated with higher tumor grade and mixed lobular/ductal breast tumor histology.

Pelvic reconstruction after abdominoperineal resection: is it worthwhile?

Abstract: The management of the perineal wound after an abdominoperineal resection (APR) has represented a challenge to surgeons. Perineal wound complications after APR have been reported to occur in 25% to 60% of cases, and rates are higher after resection of multiple visceral organs. Thus, general, oncological, colorectal, and other pelvic surgeons, in conjunction with plastic and reconstructive surgeons, have sought innovative ways to reduce perineal wound morbidity. Post-APR reconstruction of the pelvis with a vertical rectus abdominis musculocutaneous (VRAM) flap has been one such method. In this issue of Annals of Surgical Oncology, Chessin et al. report a modest-sized cohort study comparing patients who underwent reconstruction with a VRAM flap after APR with patients whose perineal wound was closed primarily after APR. All patients in both groups received preoperative chemoradiation. Perineal wound complications were significantly less frequent in the flap group than in the primary closure group (16% vs. 44%, respectively). There were no significant differences between groups in hospital stay or time to perineal wound healing. However, in patients who developed perineal wound complications, the time to perineal wound healing was shorter in the patients who had VRAM reconstruction than in those who had primary closure. The experience reported by Chessin et al. is not unique. In fact, other authors have reported similar results with musculocutaneous flaps such as the rectus abdominis, gracilis, and gluteus maximus flaps. The advantages of musculocutaneous flap reconstruction of the irradiated pelvis and perineal wound include reduction of dead space, interposition of wellvascularized, nonirradiated tissue, and replacement of resected skin. The disadvantages of these flaps include the added time for the surgical procedure, the added costs, and the potential morbidity (such as infections, flap loss, seroma, ventral and perineal hernia, and abdominal bulge) of such procedures. These disadvantages are usually offset by the lower rates of perineal wound complications. On the basis of the literature and the substantial experience with perineal reconstruction after radiation therapy at our institution, we emphatically agree that the inferiorly based VRAM flap is extremely valuable for post-APR reconstructions, for the reasons proposed by Chessin et al. In fact, its use is becoming the rule rather than the exception at our institution. As the authors point out, the VRAM flap has several advantages over unilateral or bilateral thigh-based flaps such as the gracilis musculocutaneous, posterior thigh, and anterolateral thigh flaps. These advantages include more reliable vascularity and skin viability, greater reduction of dead space, and absence of a separate donor site. Chessin et al. report several important findings in their study, particularly, the improved perineal wound healing and absence of increased overall and abdominal wall complications with the VRAM flap. An additional benefit of VRAM flap reconstruction Received November 11, 2004; accepted December 7, 2004; published online January 25, 2005.

The impact of age on post-operative outcomes of colorectal cancer patients undergoing surgical treatment

Abstract: Background the purpose of study was to evaluate the impact of age on outcomes in colorectal cancer surgery.

Japanese nationwide post-marketing survey of S-1 in patients with advanced gastric cancer.

Abstract: Background It is likely that there are some discrepancies in the safety and efficacy results for anticancer agents between those shown in registration studies for approval and those shown in clinical practice after market release. The aim of this survey was to confirm the safety and efficacy of S-1 for advanced gastric cancer after market release.

Detection of circulating cancer cells after a gastrectomy for gastric cancer.

Abstract: In this study, we evaluated the correlation between the postoperative detection of circulating cancer cells and the risk of recurrence in patients with gastric cancer. Total RNA was extracted from 1.5 ml of peripheral blood from 59 patients with gastric cancer and 15 patients with cholecystolithiasis (control) before and after operation. Carcinoembryonic antigen (CEA) messenger RNA (mRNA) was used as a probe to detect gastric cancer cells in samples using a real-time reverse transcription–polymerase chain reaction (RT-PCR). Carcinoembryonic antigen mRNA-positive cells were not found in the peripheral blood of the control patients either before or after operation, nor in the peripheral blood of the gastric cancer patients before operation. However, CEA and mRNA-positive cells were detected in 46% of the patients just after a gastrectomy, though these circulating cancer cells disappeared from peripheral blood within 2 postoperative days. In 55 patients who underwent a curative operation, the risk for cancer recurrence (10/30; 33%) in 30 patients who did not show circulating cancer cells postoperatively was higher than that for cancer recurrence (3/25; 12%) in 25 patients with positive for circulating cancer cells (P = 0.064). As a result, the presence of blood circulating tumor cells just after surgery tends to correlate with a low rate of tumor recurrence in patients operated on for gastric cancer. These findings indicate that a gastrectomy may spread gastric cancer cells into the peripheral blood from primary tumors; however, such circulating cancer cells may be destroyed within a short time. The detection of circulating cancer cells may therefore be a marker for a possibly better prognosis in patients with gastric cancer.

Early gastric cancer: concepts, diagnosis, and management.

Abstract: The incidence of gastric cancer (GC) is characterized by large geographic differences worldwide, with the lowest rates occurring in most Western industrialized countries, including the United States and the United Kingdom, and relatively high rates occurring in Japan, Korea, China, and South America. GC used to be the main cause of cancer death in Japan, but efforts have been made to promote early diagnosis. The introduction of double-contrast radiography of the stomach and developments in endoscopy have contributed to early diagnosis, and the nationwide screening system has also contributed to early detection. Early gastric cancer (EGC) now accounts for nearly 50% of all GCs treated at major institutions in Japan. EGC was defined by the Japanese Research Society for Gastric Cancer, in 1963, as adenocarcinoma of the stomach confined to the mucosa or submucosa, irrespective of lymph node involvement. Today it is recognized as a disease entity with a favorable prognosis after surgical treatment, with 5-year survival rates of over 90% reported both by Western investigators and by Japanese surgeons. The majority of reports on EGC have been from Japan, where GC is the most common malignancy. The clinicopathological features of the disease and their prognostic significance have been meticulously investigated in Japan in studies based on large numbers of cases, sometimes exceeding 1000. In the West, on the other hand, EGC remains a rare condition, and the number of EGC patients in Western series is usually small, although some European studies

A clinicopathological investigation of "tumor nodules" in colorectal cancer.

Abstract: Purpose Tumor nodules (tn) have been histologically identified within the fatty tissue or the detached fatty tissue around dissected lymph nodes, or else picked up as lymph nodes from resected specimens with no lymph node components. The TNM classification of malignant tumors provides a description of how to deal with tn, but there has so far been no description within the Japanese classification of colorectal carcinoma. The aim of this study was to determine whether we should regard tn as metastatic lymph nodes from the viewpoint of prognosis.

Clinical study of choledochocele: is it a risk factor for biliary malignancies?

Abstract: Background We aimed to clarify the clinical characteristics of choledochocele and to evaluate the possibility of choledochocele as a risk factor for biliary malignancies.