How tumor stage affects surgeons'' surveillance strategies after surgery for carcinoma of the upper aerodigestive tract

OBJECTIVE: To compare the expression of adhesion molecules on synovial T cells from patients with early spondyloarthropathy (SpA) and rheumatoid arthritis (RA), with special reference to the beta7 integrins alpha4beta7 and alphaEbeta7 in view of their intimate association with intestinal tissue. METHODS: Twenty-five synovial cell lines were generated by interleukin 2 (IL-2) expansion from synovial biopsies of patients with early SpA and RA, obtained from macroscopically inflamed synovial tissue by needle arthroscopy, and subsequently characterized by flow cytometry for CD3, CD4, CD8, L-selectin, CD11a, CD31, CD44, and alpha4beta7 and alphaEbeta7 integrin. RESULTS: In SpA, the beta7 integrin expression was increased, compared to RA. Furthermore, an inverse relation between alpha4beta7 and alphaEbeta7 was present in SpA (r = -0.75, p < 0.02), as on many mucosal T cells. In contrast, an opposite correlation was noted in RA (r = +0.84, p < 0.01), as similarly described on a subset of circulating T cells. CONCLUSION: Increased expression of beta7 integrins was noted on synovial T cell lines from SpA compared to RA, with discriminative correlations between alpha4beta7 and alphaEbeta7. This suggests a different origin of the synovial T cells in these diseases.     

Adjuvant therapy for stage II colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group

GUIDELINE QUESTION: Should patients with resected stage II colon cancer receive adjuvant therapy? OBJECTIVE: To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage II colon cancer. OUTCOMES: Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 2 members of the Provincial Gastrointestinal Disease Site Group (GI DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The recommendations resulting from this review have been approved by the GI DSG, which comprise medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this practice guideline but will do so in future guidelines development. QUALITY OF EVIDENCE: There are 25 published randomized controlled trials (RCTs) and 1 meta-analysis. The GI DSG pooled data from 11 of the 25 RCTs that provided adequate data. BENEFITS: The 25 RCTs are grouped according to the type of therapy and whether the control patients received no treatment (observation) or other adjuvant therapy after resection. Because the trials usually included patients with stage II and III cancer, the complete trial results and those for a subset of patients with stage II disease were analysed. Although the overall trial results showed a survival benefit for adjuvant treatments, the benefit was not significant for stage II patients. A meta-analysis of 11 trials comparing adjuvant treatment with observation in patients with stage II cancer indicated no significant reduction in the odds ratio (OR) for death (OR 0.83; 95% confidence interval [CI] 0.62 to 1.10). The OR for death among patients receiving chemotherapy by portal vein infusion (PVI) was 0.62 (95% CI 0.35 to 1.11). HARMS: The toxic effects of 5-fluorouracil (5-FU) with either levamisole or leucovorin, or both, were mild to moderate and consisted mostly of stomatitis, diarrhea and myelosuppression; 5% of patients required hospital admission. 5-FU plus levamisole was associated with transient neurotoxic effects in 18% of patients. Toxic effects associated with PVI were mild, rare and mostly consisted of leukopenia and diarrhea; 1% of patients experienced bowel perforation. PRACTICE GUIDELINE: Adjuvant therapy is not recommended at this time for the routine management of patients with resected stage II colon cancer. Patients with stage II disease and high-risk factors (bowel obstruction, tumour adhesion, invasion, perforation or aneuploidy) have a poorer prognosis, similar to that of patients with stage III colon cancer. For individual management, these patients should be made aware of their prognosis; treatment can be considered after the uncertainty of the value of adjuvant therapy has been explained to the patient. The enrolment of patients with high-risk stage II disease in clinical trials is encouraged. Trials comparing adjuvant therapy with observation are needed and are ethically acceptable in stage II colon cancer.     

Adjuvant therapy for stage III colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group

Brain tumors in children are a diverse group of diseases that require multidisciplinary and subspecialty expertise. Radiation therapy is an established treatment cornerstone for these pediatric tumors. Basic concepts of radiation biology and physics provide a framework for understanding the ongoing evolution in radiation delivery techniques and current treatment paradigms. Standard techniques of pediatric central nervous system radiotherapy are included in this review, as well as newer techniques including conformal therapy, stereotactic radiosurgery, and fractionated stereotactic radiotherapy. Examples are provided to illustrate differences in treatment approaches. The appropriate application of each technique is discussed, and then outcomes and treatment sequelae are compared.     

Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study

PURPOSE: The Swedish Rectal Cancer Trial has unequivocally demonstrated that preoperative high-dose (5 x 5 Gy) radiotherapy reduces local failure rates and improves overall survival. This will have an impact on the primary treatment of rectal cancer. This study investigates the effect of preoperative high-dose radiotherapy on long-term bowel function in patients treated with anterior resection. METHODS: A questionnaire was answered by 92 percent (203/220) of patients who were included in the Swedish Rectal Cancer Trial and who were alive after a minimum of five years. Thirty-two patients were excluded, mainly because of postoperative stomas and dementia, which left 171 for analysis. RESULTS: Median bowel frequency per week was 20 in the irradiated group (n = 84) and 10 in the surgery-alone group (n = 87; P < 0.001). Incontinence for loose stools (P < 0.001), urgency (P < 0.001), and emptying difficulties (P < 0.05) were all more common after irradiation. Sensory functions such as "discrimination between gas and stool" and "ability to safely release flatus" did not, however, differ between groups. Thirty percent of the irradiated group stated that they had an impaired social life because of bowel dysfunction, compared with 10 percent of the surgery-alone group (P < 0.01). CONCLUSIONS: The study indicates that high-dose radiotherapy influences long-term bowel function, thus emphasizing the need for finding predictive factors for local recurrence to exclude patients with a very high probability for cure with surgery alone and to use optimized radiation techniques.     

Recent advances in surgery for colon and rectal cancer

Surgery is the mainstay of therapy for colon and rectal cancer. Over the past several decades, there have been important advances both in the understanding of the biology of colon and rectal cancer and in the preoperative and operative techniques for treating this disease. Although it appears in some studies that we have made a difference in the survival rates in the treatment of colon and rectal cancer, in actual fact, this phenomenon may only be secondary to better staging and, therefore, a greater ability to prognosticate a particular patient's chance of cure. What has been learned in the past 20 to 30 years is that most colon and rectal carcinomas start as polyps of the colon and rectum. Most often, polyps are sporadic, but there are certain high-risk groups that produce polyps and, consequently, colon and rectal cancer at a much higher rate. The goal of a practicing physician is to identify these high-risk individuals and to recommend frequent screenings so as to intervene before a polyp has had a chance to become a deeply invasive cancer. These high-risk groups are best typified by familial adenomatous polyposis, which if left untreated will, in 100% of cases, lead to the death of a patient from colon or rectal cancer. Other diseases that lead to an increase in colon and rectal cancer but may not go through the usual adenoma-to-carcinoma sequence include inflammatory bowel disease such as Crohn's colitis and ulcerative colitis. Most patients with colorectal carcinoma are asymptomatic at the time of diagnosis. This phenomenon has led to efforts to screen the general population for polyps and for cancer. Screening techniques such as the detection of occult blood in the stool and endoscopic procedures are currently the most popular. It is unclear at this time exactly what the efficacy of these techniques is in improving the survival of the general population from colorectal carcinoma. The surgical techniques to remove colon and rectal carcinomas have recently expanded to include a more aggressive local excision policy for small tumors of the rectum and the application of laparoscopic techniques, new stapling techniques, and new anastomosing techniques for tumors of the colon and rectum. These techniques have become possible in part through advances in surgical instrumentation and also in part from our increasing understanding of the biology of the disease. Both have allowed for more creative approaches to diagnosing and treating colon and rectal cancer.(ABSTRACT TRUNCATED AT 400 WORDS)     

Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial

BACKGROUND: Colon cancer is curable by surgery, but cure rate depends on the extent of disease. We investigated whether adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer. METHODS: In a prospective randomised trial, 254 patients with colon cancer were randomly assigned postoperative ASI or no adjuvant treatment. ASI was three weekly vaccinations starting 4 weeks after surgery, with a booster vaccination at 6 months with 10(7) irradiated autologous tumour cells. The first vaccinations contained 10(7) BCG organisms. We followed up patients for time to recurrence, and recurrence-free and overall survival. Analysis was by intention to treat. FINDINGS: The 5.3 year median follow-up (range 8 months to 8 years 11 months) showed 44% (95% CI 7-66) risk reduction for recurrence in the recurrence-free period in all patients receiving ASI (p=0.023). Overall, there were 40 recurrences in the control group and 25 in the ASI group. Analysis by stage showed no significant benefit of ASI in stage III disease. The major impact of ASI was seen in patients with stage II disease, with a significantly longer recurrence-free period (p=0.011) and 61% (18-81) risk reduction for recurrences. Recurrence-free survival was significantly longer with ASI (42% risk reduction for recurrence or death [0-68], p=0.032) and there was a trend towards improved overall survival. INTERPRETATION: ASI gave significant clinical benefit in surgically resected patients with stage II colon cancer. ASI has minimal adverse reactions and should be considered in the management of stage II colon cancer.     

Surveillance after colorectal cancer surgery

Early diagnosis of local and distant recurrences of colorectal cancer remains difficult and there is no agreement on the effectiveness of follow-up in these patients. The aim of this study is to assess the value of our method of follow-up. We consider 239 patients with colorectal cancer and at least 2 years follow-up following radical resection. A local recurrence appeared in 26 patients (10.9%), a distant metastasis in 41 (17.1%), while in seven (2.9%) local and distant recurrences appeared simultaneously. Local recurrence was detected because of an increase in carcinoembryonic antigen (CEA) level in 15 patients (57.7%), during a scheduled endoscopy in four (15.4%) and because of symptoms in seven (26.9%). In seven patients (26.9%) a radical resection was possible. Distant metastases were detected by CEA levels in 20 patients (48.8%), by ultrasonography (U.S.) in 12 (29.3%) and by chest X-ray in five (12.2%). In 13 of 26 patients with liver metastases a resection was performed. This study shows that few patients benefit from follow-up and only CEA levels and liver U.S. performed intensively between 15 and 36 months after surgery are useful in early detection of recurrences. A modification of the follow-up to the single patient, according to the stage, location and grading of cancer, could improve the results, so lowering the costs of this expensive practice.     

Possible effect of pneumoperitoneum on the spreading of colon cancer tumor cells

Development of the central somatosensory system is profoundly modulated by the sensory periphery. Cauterization of facial whiskers alters the segregation pattern of barrels in rodents only during a few days just after birth (critical period). Although a molecular basis of the segregation of barrel neurons and the critical period for the anatomical plasticity observed in layer IV barrel neuron is not clear yet, the accumulating evidence suggests that neurotrophins modulate synaptic connections including central nervous system. In this study, we showed by in situ hybridization that mouse barrel side neurons express brain-derived neurotrophic factor (BDNF) mRNA and both catalytic and non-catalytic forms of trkB mRNA. Cautery of row C vibrissae on the right side of the face within 24 h after birth (post natal day 0, PND0) reduced the expression of BDNF and trkB mRNA from the division region between the contralateral row C barrels at PND7. The vibrissae in row A, C, and E were cauterized at PND0 followed by quantitative RT-PCR for BDNF and trkB mRNA with total RNA isolated from the barrel region at PND7. The result showed that BDNF, but not trkB, mRNA was increased several-fold in the contralateral barrel region. These data suggest that the expression of BDNF mRNA is differentially regulated between injured barrels and actively innervated barrels. The differential expression of the mRNA encoding neurotrophins and their receptors may be important in regulating the injury-dependent re-segregation of barrels.     

Autologous breast reconstruction after breast-conserving cancer surgery

Breast-conserving therapy, which aims to reduce trauma by preserving as much of a patient's natural appearance as possible, does not necessarily lead to an optimal cosmesis. We hypothesized that combining plastic and oncologic surgeries would greatly reduce the physical and psychological traumas and produce an optimal cosmesis without impairing the oncologic outcome. We performed breast reconstruction on 40 cancer patients. Of those 40 patients, 15 received combined plastic and oncologic surgeries. Procedures depended on breast size: mammareduction plasty in cases with sufficient volume, and reconstruction using myocutaneous latissimus dorsi flaps for those with less volume. Cosmetic results were rated good to poor. Of the 15 primary reconstruction patients, 86.7 percent of the cases showed good results and 13.3 percent fair; in the secondary cases, 68 percent were good, 16 percent fair, and 16 percent poor. Through a follow-up and cosmetic evaluations by both surgeons and patients, the study showed that combining aesthetic improvements and oncologic surgery does not compromise patient safety, reduces mental and physical trauma, and frequently results in superior cosmesis, thereby improving the patient's overall health.     

Liver metastases from colon cancer with intra-bile duct tumor growth: radiologic features

PURPOSE: Our goal was to characterize the radiologic features of liver metastases from colon cancer with intrahepatic bile duct (IHBD) dilatation. METHOD: Radiologic findings of liver metastases from colon cancer with IHBD dilatation of four patients were compared with pathologic findings. RESULTS: The cause of bile duct dilatation in all cases was due to papillary tumor growth in the bile duct. In two patients, intra-bile duct tumor growth (IBDTG) was observed on imaging. In the other two patients, IBDTG was not observed, but a nontapered abrupt obstruction of a dilated bile duct was seen, corresponding to the microscopically proven papillary tumor growth in the ductal lumen. In three patients who underwent an extensive hepatic resection, there has been no recurrence. In one patient who had a nonanatomic limited resection, a recurrence was seen 1 year after surgery. CONCLUSION: When liver tumor with IBDTG is suspected on imaging, liver metastases should be considered in the differential diagnosis besides hepatocellular carcinoma or cholangiocellular carcinoma. Careful preoperative assessment for IBDTG by imaging is essential to determine the extent of surgical resection.     

Progression detection of stage I nonseminomatous testis cancer on surveillance: implications for the followup protocol

PURPOSE: To optimize followup in patients with stage I nonseminomatous testis cancer on surveillance we evaluated the contribution of each followup modality to the detection of progression as well as morbidity and mortality outcomes. MATERIALS AND METHODS: After orchiectomy 170 patients with clinical stage I nonseminoma were prospectively placed on a surveillance protocol. History, physical examination, serum tumor markers, abdominal and pelvic computerized tomography (CT), and chest x-ray were used for followup. The number of failures, methods and timing of progression detection, treatments required, mortality rate and subsequent contralateral primary tumors were recorded. RESULTS: The 170 surveillance patients were followed a median of 6.3 years. Within 2 years (median 6.9 months) postoperatively 48 patients (28.2%) had disease progression. History, physical examination, markers, CT and chest radiography provided the initial evidence of progression in 18 (37.5%), 34 (70.8%), 34 (70.8%), and 4 (8.3%) patients, respectively. Each modality was the only indicator of failure in 2 (4.2%), 4 (8.3%), 10 (20.8%) and 0 cases, respectively. Of the 170 patients 122 (71.8%) required no additional treatment beyond orchiectomy, 26 (15.3%) received 1 and 22 (12.9%) underwent more than 1 therapeutic modality. Only 1 patient (0.6%) died of disease. Contralateral tumors developed in 5 cases (2.9%) therapeutic a mean of 8.1 years after orchiectomy. CONCLUSIONS: In stage I nonseminoma patients, surveillance history, physical examination, tumor markers and abdominopelvic CT are necessary components of the followup protocol. Removal of routine chest x-ray from the protocol would not have changed progression detection. The initial surveillance visit must occur by 2 months postoperatively. Patients should be followed beyond 5 years and likely for life in addition to regular patient self-examination.     

Adjuvant therapy after primary surgery for stage I-IIA carcinoma of the cervix

Radical hysterectomy and bilateral pelvic lymph node dissection is commonly used as a primary management option for treatment of stage IB/IIA carcinoma of the cervix. Overall cure rates approach 85%. However, a spectrum of relapse risk exists, depending on the presence or absence of primary tumor and nodal-related prognostic factors. Known factors include number and location of lymph nodes; size of primary, deep invasion in the cervix; capillary lymphatic space involvement; occult parametrial involvement; and positive or close surgical margins. Biologic determinants have yet to be identified. No systematic analysis has examined various combinations of prognostic factors to precisely define associated levels of risk and to predict the sites of relapse. Decreased local control and survival rates in some high-risk subgroups, usually those with nodal positivity, has led to the exploration of adjuvant therapies. Compiled data from retrospective series have defined the overall patterns of failure. Seventy-two percent of those relapsing have a component of pelvic failure, while 42% experience relapse in the pelvis alone. Fifty-eight percent have a component of distant failure but only 28% have distant disease alone. Adjuvant treatment options include pelvic radiotherapy, extended-field radiotherapy, chemoradiotherapy, and chemotherapy. Trials of adjuvant chemotherapy are too few to evaluate the use of available agents. Pelvic radiotherapy has been shown to reduce the relapse risk when surgical margins are close or positive. It also reduces the risk of pelvic relapse and improves the relapse-free interval but has no apparent impact on overall survival in the groups that have been selected for treatment. The apparent lack of benefit may relate to the choice of patients with nodal involvement who, despite high risk of pelvic failure, most likely have a predominant pattern of distant failure. Maximization of the survival benefit of pelvic radiotherapy requires the identification and treatment of the subgroup with a predominant pattern of pelvic failure, such as that examined in Gynecologic Oncology Group protocol 92. These may be patients with primary tumor-related, high-risk factors but negative nodes. Extended-field irradiation for microscopically involved para-aortic nodes provides a cure in 25%-40% of the patients. Further studies of prognostic factors and their relationship to sites of failure after surgery are necessary to define the benefits of currently available adjuvant therapies with respect to local control, survival, and quality of life, and also to direct future studies. New, effective systemic agents are required for those at high risk of developing distant disease.     

Primary colon cancer without gross mucosal tumor: unusual presentation of a common malignancy

Colon cancer typically arises in the colonic lumen, allowing for endoscopic detection of cancerous and premalignant lesions. In the case presented, a 73-year-old man with iron deficiency anemia had two colonoscopies showing only diverticula and internal hemorrhoids. Three years later, when the patient complained of dull, intermittent lower abdominal pain, a third colonoscopy identified diverticula, three adenomatous polyps, and no other abnormality. Computed tomography (CT) of the abdomen revealed a 5 cm x 6 cm pericolic fluid collection, which was later found to communicate with the sigmoid colon. The surgical specimen from a partial colectomy contained a distal sigmoid perforation with a 2.5 cm moderately differentiated adenocarcinoma in the underlying submucosal tissue. There was no gross intraluminal tumor. Histopathology, including immunohistochemistry, was consistent with colonic adenocarcinoma. Primary colon cancer grossly sparing the mucosa is an unusual presentation for this common malignancy.     

Early stage vocal cord cancer: results after external beam radiotherapy

Much has been written about suck confusion due to a baby's oral experience with objects other than the breast--but how much difference is there in the relative impacts on a baby's ineffective suck if a teat is used instead of other currently accepted techniques such as cup and finger feeding? Mothers who seek the help of a lactation consultant will commonly already be using bottles and teats as part of their management regime for a difficult situation. Especially if the problems are well developed and complex, many mothers will not be able to accept unfamiliar alternatives such as cup and finger feeding and prefer to wean rather than do so. Current teat designs have evolved with no reference to Woolridge's landmark research published over ten years ago which clearly demonstrated how normal breastfeeding works. Rather, manufacturers offer consumers an array of teats which have been shortened in length and distorted in conformation when compared with teats available thirty years ago which coincidentally were a closer physiological match with the positioning of the nipple and breast tissues in the mouth of a breastfeeding baby than teats designed and produced since then. Fortunately one UK manufacturer still markets this thirty year old style of teat in a flow rate suitable for very young babies. Over a three year period, we at first hesitantly, but with increasing confidence asked mothers to use this teat when suck retraining and supplementation were indicated. We are able to report that use of these teats has resulted in a success rate in excess of 90% converting babies with significant sucking problems into fully effective breastfeeders.     

Salvage surgery after unsuccessful radiotherapy of laryngeal cancer]

The methods usually employed for reconstruction of total lower eyelid loss include (1) tarsoconjunctival flaps from the upper eyelid and skin-graft cover and (2) chondromucosal grafts and local skin-flap cover. We report a technique for coverage of these defects with an island flap involving the full thickness of the ipsilateral nasal wall based on the dorsal (external) nasal vessels, terminal branches of the ophthalmic vessels. The advantages of this method are (1) the main components of the eyelid (skin, tarsus, conjunctiva) are reconstructed in a single short operation, even under local anesthesia, (2) there is one donor area that can be closed primarily without significant deformity, (3) the upper lid remains intact, and ectropion is improbable, and (4) the procedure involves a short hospitalization. As disadvantages we might mention bulkiness of the new eyelid and difficult dissection of the (subcutaneous) pedicle.     

Severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery

Tamoxifen, a nonsteroidal estrogen antagonist, has been widely used in a hormonal treatment for breast cancer. The side effects of tamoxifen are generally recognized to be mild. However, we experienced three cases of severe hypertriglyceridemia and/or hyperglycemia induced by tamoxifen. For normalization of their hypertriglyceridemia we need to stop giving tamoxifen. In one of three cases we analyzed her lipoprotein profile in detail with lipoprotein lipase activities and apolipoprotein E phenotype. The case was a 49 year-old woman. After 15 months of tamoxifen administration, she was diagnosed as severe hypertriglyceridemia. Consecutively, severe hyperglycemia was occurred to need insulin therapy. After tamoxifen withdrawal, her triglyceride and glucose levels improved. Her lipolytic enzyme was reduced during tamoxifen treatment. Apolipoprotein E phenotype was uncommon E4/2. Although hypertriglyceridemia was not considered to be a risk factor for coronary heart disease, a marked hypertriglyceridemia might occasionally produce severe lethal pancreatitis. We recommend that a periodic plasma lipid analysis is needed for patients treated with tamoxifen, especially for diabetic and hypertriglyceridemic patients, to avoid such complications.