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Sexual dysfunction, informed consent and multimodality therapy for rectal cancer.

BACKGROUND: This study assessed the presurgical and preradiation discussion of the risk of posttherapy sexual dysfunction among patients who underwent potentially curative therapy for rectal cancer. The incidence of sexual dysfunction after treatment for rectal cancer was then determined. METHODS: A retrospective review of the medical records of 52 consecutive patients who underwent potentially curative procedures for rectal cancer within 15 cm from the anal verge was performed. RESULTS: Presurgical discussion of the risk of sexual dysfunction was not documented in the consent in 37 of 52 patients (71%). Among the 5 males who underwent local excision, none reported posttherapy sexual dysfunction. Of the 6 males who were treated by low anterior resection, only 1 had a postoperative complaint of sexual dysfunction. Five of 15 males (33%) treated with abdominoperineal resection (APR) alone reported postprocedure sexual dysfunction, whereas 6 of 8 males (75%) treated with APR and radiation reported dysfunction. Of the entire female cohort, only 1 of the 16 reported sexual dysfunction posttherapy. CONCLUSION: A discussion of the risks of posttherapy sexual dysfunction was documented for fewer than one third of the patients. Among males after APR, the use of postoperative radiation showed a trend toward an increase in sexual dysfunction. Surgery and/or radiation therapy did not impact on sexual dysfunction in females.

Adult↗

Multimodality preoperative treatment for advanced stage IV (MO) cancer of the head and neck.

Sixty-three patients with advanced unresectable squamous cell carcinoma of the head and neck were treated with a combination of chemotherapy, radiation, and surgery. We observed a 75% response to neoadjuvant chemotherapy. The 5-year survival rate for all 63 patients was 20%, and only 3 patients were alive at 8 years. The 5-year survival rate for patients who completed the treatment plan and received chemotherapy, radiation, and surgery was 43% compared with 20% for those who had chemotherapy and radiation but refused surgery. Development of a second primary cancer was the cause of death in 62% of the patients who survived more than 24 months.

Carcinoma, Squamous Cell↗

Multimodal therapy in locally advanced breast carcinoma.

Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of metastatic carcinoid tumors using multimodality therapy of octreotide acetate, intra-arterial chemotherapy, and hepatic arterial chemoembolization.

BACKGROUND: Overall survival and quality of life in patients with metastatic carcinoid tumors depend on control of tumor growth and suppression of amine-induced symptoms. METHODS: We report on a series of 10 patients with carcinoid tumors metastatic to the liver who were treated with long-term octreotide acetate therapy (100 to 500 micrograms three times a day), sequential intra-arterial 5-fluorouracil (5-FU) infusions, and hepatic tumor chemoembolization. RESULTS: All 10 patients remained asymptomatic or had extremely mild symptoms after combined modality therapy (mean follow-up duration of 51.5 months). Sixty percent of the patients had a > 50% reduction of their tumor size (mean duration 42 months). An additional 30% experienced stabilization of tumor growth for 6 months or longer. Five of the 10 patients are currently alive. The mean group survival is 58 months since diagnosis (range 33 to 115) and 40 months since starting therapy (range 12 to 65). CONCLUSIONS: Combining octreotide acetate, intra-arterial 5-FU, and tumor chemoembolization effectively retards tumor growth while providing excellent symptom control.

Aged↗

Percutaneous endoscopic gastrostomy before multimodality therapy in patients with esophageal cancer.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has not been widely used in esophageal cancer because of concerns about safety of dilatation, suitability of the stomach as an esophageal replacement, and potential for inoculation metastasis. METHODS: Experience with PEG in consecutive patients presenting with new esophageal cancer from March 1991 to March 2001 was reviewed retrospectively. PEG was planned in 119 of 179 (66%) of these patients excluding those presenting moribund and those for whom early resection was planned. The PEG was placed using an endoscopic method with wire-guided endoscopic bougienage or laser ablation or both as needed. Success of placement, requirement for dilatation and ablation, PEG-related complications, tolerance of enteral feeds, and impact on therapy were evaluated. RESULTS: PEG placement was possible in 87% of patients (103 of 119). Dilatation or laser ablation or both was required in 46% (47 of 103). There was no procedure-related mortality. Thirty-day mortality was 13.5%. Major PEG-related complications were observed in 4% (4 of 103) and minor PEG-related complications in 12% (12 of 103). PEG removal was required in 4 patients and interruption of enteral feeds required in 33 (32%). No instances of esophageal disruption or tumor inoculation metastasis were noted. PEG takedown and site closure at the time of operation was uncomplicated and use of the stomach as an esophageal substitute was possible in all 61 resected patients. Rates of anastomotic leak, stricture, and gastric emptying delay were similar to those for patients proceeding to resection without prior PEG (leak: PEG = 8% [5 of 61] versus non-PEG = 10.5% [2 of 19]), (stricture: PEG = 37% [22 of 61] versus non-PEG = 32.5% [6 of 19]), (delay: PEG = 9.8% [6 of 61] versus non-PEG = 10.5% [2 of 19]). Analysis of variables showed PEG to be significantly related to attainment of target doses of chemoradiotherapy (p = 0.034), and survival at 12 months (p = 0.02). CONCLUSIONS: PEG in esophageal cancer is safe and useful and does not compromise the stomach or esophagogastric anastomosis. Further study is required to define the efficacy of PEG as a means of nutritional support and its impact on survival.

Adult↗

Aggressive multimodality therapy for stage III esophageal cancer: a phase I/II study.

BACKGROUND: Stage III advanced locoregional esophageal carcinoma is frequently unresectable and inconsistently represented in therapeutic trials of esophageal cancer. METHODS: From 1992 to 1998, 34 of 131 total esophageal cancer patients were designated stage III (16 T3N1, 9 T4N0, 9 T4N1) and medically fit to enter a combined modality protocol with continuous infusion 5-fluorouracil (CIS-FU, 300 to 600 mg/m2/day), high-dose external beam irradiation (60 Gy), and interval esophagectomy. Staging before and after induction therapy included computed tomography; endoscopy, and endoscopic ultrasound. RESULTS: Significant toxicity from induction therapy included death (5/34; 14.7%), pneumonitis (5/34; 14.7%), mucositis (13/34; 38%), and hand-foot syndrome (3/34; 8.8%). In addition to the five deaths, 11 patients did not proceed to operation because of development of esophagorespiratory fistula in 3, distant disease in 2, persistence of T4 stage in 2, progression of comorbidities in 2, and patient refusal in 2. There was a discrepancy between clinical complete response (cCR) at restaging 56% (19/34) and pathologic CR (pCR) noted at the time of operation (8/34; 23.5%). Complete resections were possible in 16 of 18 patients explored. Complications in 4 patients included: death (1), airway injury (1), chylothorax requiring reoperation (1), anastomotic leak (1), recurrent nerve injury with vocal cord paresis (2), and ascaris infection (1). Actuarial survival analysis using the Kaplan-Meier method and log-rank testing showed a 36-month survival of 20% for the group as a whole and 27% for patients restaged cCR (cCR vs PR, p = 0.0046). Treatment failure is predominantly distant, with good local control in resected patients. N0 node status was strongly associated with survival (N0 vs N1 p = 0.0024). There is a trend towards improved survival in the resected group (resected 22% vs nonresected 10% at 3 years, p = 0.17). CONCLUSIONS: Response rates and survival are commensurate with multiple completed phase II and III trials. These are attained at a higher treatment-related mortality. T4 patients can be successfully resected in selected patients. Even in advanced disease, nodal status is a significant predictor of survival.

Adenocarcinoma↗

Multimodal action of single Na+ channels in myocardial mouse cells.

Unitary Na+ currents of myocardial mouse cells were studied at room temperature in 10 cell-attached patches, each containing one and only one channel. Small-pore patch pipettes (resistance 10-97 M omega when filled with 200% Tyrode's solution) with exceptionally thick walls were used. Observed were both rapidly inactivating (6 patches) and slowly inactivating (3 patches) Na+ currents. In one patch, a slow transition from rather fast to slow inactivation was detected over a time of 0.5 h. A short and a long component of the open-channel life time were recorded at the beginning, but only a short one at the end of the experiment. Concomitantly, the first latency was slowed. Amplitude histograms showed that the electrochemical driving force across the pore of the channel did not change during this time. In three patches, a fast and repetitive switching between different modes of Na+ channel action could be clearly identified by plotting the long-time course of the averaged current per trace. The ensemble-averaged current formed in each mode was different in kinetics and amplitude. Each mode had a characteristic mean open-channel life time and distribution of first latency, but the predominant single-channel current amplitude was unaffected by mode switches. It is concluded that two types of changes in kinetics may happen in a single Na+ channel: fast and reversible switches between different modes, and a slow loss of inactivation.

Animals↗

[Fast-track multimodal rehabilitation programs in laparoscopic colorectal surgery].

For the last two decades, general and digestive surgeons have attempted to improve the postoperative course of surgical patients. Classical perioperative treatment can be described as a period of preoperative dehydration caused by fasting and intensive colon preparation followed by fluid overload generally due to excessively prolonged serum therapy. There is also perioperative surgical stress, the trauma of surgery itself, and a long period of drainage and nasogastric tubes. The patient is thus literally confined to bed and mobilization is, at the very least, difficult. Moreover, the use of opiates delays intestinal peristalsis and consequently oral nutrition. All together, these factors prolong the length of hospital stay and hamper recovery. All these perioperative treatment modalities have been questioned by Kehlet, resulting in a set of new, more realistic and evidence-based modalities, currently known as the fast-track program. The aim of this program is to decrease perioperative stress, reduce organ involvement produced by surgical trauma and hasten the patient's general recovery. Major advantages of this program consist not only of shorter length of hospital stay but also of a concurrent improvement in patients' quality of life and a reduction in mortality. The present review article analyzes all these modalities, with special emphasis on laparoscopic colorectal surgery. This approach is presented as one of the elements of the fast-track program.

Anesthesia, Conduction↗

Tool-use changes multimodal spatial interactions between vision and touch in normal humans.

In a visual-tactile interference paradigm, subjects judged whether tactile vibrations arose on a finger or thumb (upper vs. lower locations), while ignoring distant visual distractor lights that also appeared in upper or lower locations. Incongruent visual distractors (e.g. a lower light combined with upper touch) disrupt such tactile judgements, particularly when appearing near the tactile stimulus (e.g. on the same side of space as the stimulated hand). Here we show that actively wielding tools can change this pattern of crossmodal interference. When such tools were held in crossed positions (connecting the left hand to the right visual field, and vice-versa), the spatial constraints on crossmodal interference reversed, so that visual distractors in the other visual field now disrupted tactile judgements most for a particular hand. This phenomenon depended on active tool-use, developing with increased experience in using the tool. We relate these results to recent physiological and neuropsychological findings.

Adult↗

Automated registration of multimodal brain image sets using computer vision methods.

We present a new method of registering three dimensional image volumes of the brain of a given patient acquired at different times or with different imaging modalities, or both. Registration is an essential requirement for fusing the data from the two image sets so as to either increase the available information by exploiting complementary imaging modalities, or to measure small changes over time for prognostication, disease assessment, etc. The new technique exploits an external, removable, remountable reference frame which is attached to the head. Computer vision techniques are used to determine the positions of fiducial marks in every image. The transformation required to map each image of one image volume onto the other image volume is developed using the theory of quaternions. The results indicate that the new technique is robust and practical in a clinical setting.

Algorithms↗

The role of multimodal therapy in patients with local and regional neuroblastoma.

The records of 49 patients with local and regional neuroblastoma treated at The Children's Hospital of Philadelphia between 1972-1981 were reviewed to determine the contribution of radiation therapy and chemotherapy to their management. All 11 state I patients were treated with surgery alone and 10 (91%) survived for periods ranging from 3 to 10 years. Half of the 24 stage II patients received radiation therapy with or without chemotherapy and 8/12 (67%) survive. Ten of the 12 remaining stage II patients survive (83%) following surgery alone. All stage II patients had residual disease and 13 had involvement in lymph nodes. 7 in the combined treatment group and 6 in the surgery alone group. All 14 stage III patients received postoperative chemotherapy and radiation therapy (RT) and 7 or 50% remain disease free. We conclude that surgery alone is sufficient for patients with stage I NBL, that RT and chemotherapy do not appear to alter the outcome in stage II patients, and better methods of therapy are needed for patients with stage III disease.

Adolescent↗

Multimodality treatment of complex renal calculi.

More than 2,500 patients were treated for urolithiasis from 1984 to 1987. In an effort to define the relative role of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy with respect to size, location and composition of the calculus 912 of these patients (224 of whom underwent percutaneous nephrolithotomy and 688 of whom underwent extracorporeal shock wave lithotripsy) were reviewed. Size proved to be the only significant factor in the success and complication rates of extracorporeal shock wave lithotripsy but it did not affect the outcome of percutaneous nephrolithotomy. The roles of these 2 modalities were then examined with respect to the treatment of complex renal calculi. We reviewed 376 patients with complex renal calculi, including 40 percutaneous nephrolithotomy patients from the initial 912 patients studied. The initial therapy in 100 of these patients, treated consecutively, was extracorporeal shock wave lithotripsy. The remaining 276 patients were treated by percutaneous nephrolithotomy. The success rate of extracorporeal shock wave lithotripsy monotherapy in the treatment of complex renal calculi was 36%. The success rate of primary percutaneous nephrolithotomy was 83%. We conclude that percutaneous nephrolithotomy should be the primary therapy for patients with complex renal calculi. Extracorporeal shock wave lithotripsy is the preferred treatment for patients with smaller calculi and as an adjunct to percutaneous nephrolithotomy.

Combined Modality Therapy↗

Multimodal treatment of advanced testicular tumor with radical reductive surgery and multisequential chemotherapy with cis platinum, bleomycin, vinblastine, vincristine and actinomycin D.

Advanced testicular tumors in 34 patients were treated by combination chemotherapy with bleomycin, vinblastine, vincristine, cis platinum and actinomycin D. The therapy was divided into 3 phases: 1) induction, 2) consolidation and 3) maintenance. Induction lasted 4 weeks and consisted of 420 mg. bleomycin, 0.2 mg./kg. vinblastine, 4 mg./kg. cis platinum, and 20 mg. prednisone daily. Consolidation lasted 6 weeks and consisted of 5 mg. actinomycin D, 6 mg. vincristine and 6 mg./kg. cis platinum. Maintenance therapy was achieved with 2.5 mg. actinomycin D every 6 weeks and 1 mg./kg. cis platinum every 3 weeks. A tumor reductive operation was done before induction of chemotherapy in 13 patients and after induction of chemotherapy in 12 patients. Nine patients were treated with chemotherapy alone. Three patients with brain metastases received concomitant radiotherapy to the brain (3,000 rads). A previous operation and chemotherapy had failed in 11 patients and previous radiotherapy had failed in 1 patient. All patients treated had at least 1 objective response (34 of 34 or 100 per cent). Partial clinical remission was achieved in 7 of 34 patients (21 per cent). A complete clinical remission was observed in 27 of 34 patients (79 per cent) and of this group 6 had a relapse. At present, 22 of 34 patients are free of disease from 4 to 24 months, with an average of 13 months (65 per cent). The toxicity consisted of nausea, vomiting, mucositis, alopecia, mild leukopenia and tinnitus. This approach seems to be effective in producing long clinical remissions in the majority of patients with advanced disease.

Adolescent↗

Multimodal visual-somatosensory integration in saccade generation.

Neurophysiological studies have demonstrated multisensory interaction effects in the neural structures involved in saccade generation when visual, auditory or somatosensory stimuli are presented bimodally. Visual-auditory interaction effects have been demonstrated in numerous behavioural studies of saccades but little is known about interaction effects involving somatosensory stimuli. The present study examined visual-somatosensory interaction effects on saccade generation using a multisensory paradigm, whereby task-irrelevant distractors appeared spatially-coincident with, or remote from the designated saccade target. Somatosensory distractors reduced the latency of saccades when presented before the visual target and the greatest facilitation effect was observed with spatially-coincident stimuli. Visual distractors spatially-coincident with a somatosensory target reduced latency (and increased peak velocity) when presented before and after the target. Visual distractors contralateral to somatosensory targets increased saccade latency and produced high error rates of saccades made to the distractor. The high error rates and latency modulation with visual distractors is consistent with a bias for visual stimuli in the saccadic system. In the visual target condition, saccade latency was modulated by a somatosensory distractor that was entirely task-irrelevant and this effect was always greatest with spatially-coincident distractors. The multisensory distractor effects are discussed in terms of saccades being programmed to the non-target modality, the early triggering of a non-spatial saccade 'when' signal, and multisensory neuronal enhancement effects.

Acoustic Stimulation↗