bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting Surgical Wait Times for Breast Reconstruction
Authors: U Boyd Kirsty , Lf Temple Claire , C Ross Douglas
Published: February 2017

OBJECTIVE

To examine factors that affect wait times for women seeking breast reconstruction at a Canadian academic centre.

METHODS

A retrospective audit of 57 women seeking breast reconstruction over a three-year period was completed. Comparisons of wait times were made considering the surgical pathology, timing of reconstruction (immediate versus delayed), urgency of pathology, method of reconstruction (implant versus autologous) and the number of surgeons involved. Specifically, the wait times from referral to specialist consultation, consultation to surgery, and referral to surgery were examined.

RESULTS

Women with active cancer (ductal carcinoma in situ: 43 days, invasive cancer: 40 days) had shorter wait times compared with those who had no active cancer (benign/high risk: 242 days, previously treated cancer: 343 days) (P<0.05). Women seeking delayed reconstruction had longer wait times (359 days) from referral to surgery than women seeking immediate reconstruction (98 days) (P<0.0001). Women seeking reconstruction at the time of mastectomy, with benign/high-risk disease, waited longer (242 days) than those with ductal carcinoma in situ (43 days) or invasive cancer (40 days) (P<0.001). Wait times for autologous free tissue transfer (213 days) were not significantly longer compared with implant reconstruction (116 days) (P=0.27). Women with acute cancer experienced similar wait times for implant reconstruction (44 days) as for a free tissue transfer (56 days) (P=0.46). Women with no acute cancer had similar wait times for implant (239 days) as free tissue transfer (369 days) (P=0.25). Patients requiring only plastic surgeons involved in the reconstructive effort waited longer (one surgeon: 299 days, two surgeons: 550 days) than patients requiring either two plastic surgeons and one general surgeon (130 days) or one plastic surgeon and one general surgeon (82 days) (P<0.05). Although more coordination is required with three surgeons, this is frequently associated with a diagnosis of acute cancer and, therefore, wait times are shorter.
Reconstruction of a Full-Thickness Alar Wound Using An Auricular Conchal Composite Graft
Authors: Klinger Marco , Maione Luca , Villani Federico , Caviggioli Fabio , Forcellini Davide , Klinger Francesco
Published: February 2017

Nasogastric intubation has become a frequently used method for alleviating gastrointestinal symptoms. Necrosis from alar pressure during prolonged nasogastric and nasotracheal intubation is common, and can result in considerable deformity if it is unrecognized. The reconstruction of full-thickness alar wounds often requires multiple challenging surgical procedures. Difficult full-thickness alar defects often require nasal mucosal replacement for lining, cartilage batten graft support for the preservation of nasal function, and skin coverage for the restoration of an aesthetically correct appearance. Free composite conchal grafting can offer a single-staged, one-step repair of difficult full-thickness alar wounds that are no larger than 1.5 cm in size. A thorough explanation of the graft design and execution is presented, as well as a case report and literature review. Free composite con-chal grafting can produce aesthetic and functional results that rival the most sophisticated flap reconstructions of the lateral ala.
An Investigation of the Application of Laser-Assisted Indocyanine Green Fluorescent Dye Angiography in Pedicle Transverse Rectus Abdominus Myocutaneous Breast Reconstruction
Authors: Newman Martin I , C Samson Michel , F Tamburrino Joseph , A Swartz Kimberly , Brunworth Louis
Published: February 2017

BACKGROUND

Pedicle transverse rectus abdominus myocutaneous (pTRAM) flaps remain the most common method of autologous tissue breast reconstruction. Using pTRAM flaps, complications often arise postoperatively, secondary to inadequate circulation. Tissues from distant angiosomes are associated with poorer perfusion, but this differs among patients. Many modalities have been used to reduce the risk of complications, but none have achieved widespread application. The authors believe that laser-assisted indocyanine green fluorescent dye angiography (LA-ICGA) can potentially reduce the risk of complications.

METHODS

In two routine, single-pedicle, ipsilateral pTRAM flaps, LA-ICGA imaging was performed following the division of the distal rectus muscle and deep inferior epigastric pedicle. The resulting images were used to guide design of the flap and debridement.

RESULTS

In case 1, good perfusion was observed in zone 1 and part of zone 2. In case 2, good perfusion was observed in zone 1 and 50% of zone 3, with little perfusion in zone 2. In both cases, tissues with poor perfusion were debrided before transfer and inset. In both patients, there were no issues with wound healing, tissue necrosis or fat necrosis.

CONCLUSIONS

The variability of perfusion of the pTRAM flap among individuals is well appreciated. LA-ICGA helped to determine the limits of good perfusion and, therefore, the limits of tissue to be preserved for transfer and inset. This helped to avoid harvesting poorly perfused tissue that would have almost certainly experienced necrosis and, ultimately, would have reduced the risk of postoperative complications.
Giant Cell Reparative Granuloma of the Proximal Phalanx: A Case Report and Literature Review
Authors: Perkins A , Izadpanah A , Sinno H , Bernard C , Williams Hb
Published: February 2017

The present article is a case report of a 16-year-old boy who presented with a benign bony tumour, which on histological analysis suggested giant cell reparative granuloma (GCRG), but was not corroborate by blood tests. The implications of this type of tumour and the correct diagnostic requirements were investigated. The correct identification of GCRG from other giant cell-containing tumours is important because the treatment modalities for these tumours significantly differ from one another. In most cases, histological findings are sufficient to identify the tumours. In most GCRG cases, curettage is usually a curative treatment option. However, due to high recurrence rates of GCRGs, close follow-up of these patients is warranted. Also, due to osteoclastic activity of the giant cells in GCRGs, the use of drugs such as calcitonin or bisphosphonates, which inhibit osteoclast differentiation and activation, may have an important influence on future treatments or in reducing the recurrence rate of these tumours.
How acidic is the lidocaine we are injecting, and how much bicarbonate should we add?
Authors: Frank Simon G , Lalonde Donald H
Published: February 2017

Background

The infiltration of local anesthetics can be painful, which is likely due, in part, to their acidity. In spite of a Cochrane study that recommended neutralizing lidocaine with bicarbonate to decrease the pain of injection, not many surgeons have adopted the practice, and there are many ‘recipes’ for how much bicarbonate one should add.

Objective

To determine the acidity of lidocaine and the correct ratio of bicarbonate that should be added to neutralize lidocaine to achieve body pH.

Methods

Fifty samples each of commonly used anesthetics (lidocaine 1% and 2%, with and without epinephrine 1:100,000) were obtained and tested for pH. Data were also analyzed according to whether the vials had been previously opened. Ten additional samples of lidocaine 1% with 1:100,000 epinephrine were titrated against sodium bicarbonate 8.4% and tested for pH and the presence of precipitate.

Results

A solution of 1% lidocaine with 1:100,000 epinephrine had a mean (± SD) pH of 4.24±0.42, and 2% lidocaine with 1:100,000 epinephrine had a mean pH of 3.93±0.43. Plain 1% lidocaine had a pH of 6.09±0.16, and plain 2% lidocaine had a pH of 6.00±0.27. Epinephrine-containing solutions were more acidic when they had been previously opened. One per cent lidocaine with epinephrine required 8.4% sodium bicarbonate at a ratio of 1.1 mL:10 mL to 1.8 mL:10 mL to achieve the target tissue pH of 7.38 to 7.62.

Conclusion

Lidocaine with epinephrine was approximately 1000 times more acidic than subcutaneous tissue. The addition of bicarbonate to the local anesthetic solution is simple to perform and is inexpensive. The proper volume ratio of 8.4% sodium bicarbonate to 1% lidocaine with 1:100,000 epinephrine is approximately 1 mL:10 mL. Surgeons should be more aware of the simplicity and value of buffering with bicarbonate to decrease the pain of injection.
Reduction mammoplasty improves body posture and decreases the perception of pain
Authors: Goulart Remi , Detanico Daniele , Vasconcellos Roberta Pires , Schütz Gustavo Ricardo , dos Santos Saray Giovana
Published: February 2017

Women with hypertrophic breasts often experience body pain and posture problems, which tend to be reduced or even eliminated after reduction mammoplasty. The present study aimed to analyze the effects of reduction mammoplasty on anthropometric variables, body posture and pain in women with breast hypertrophy. Eleven women (mean [± SD] age 31.3±10.4 years) participated in the present study. Anthropometric variables, body posture and pain perception were evaluated pretest, and 60 (post60) and 90 (post90) days after reduction mammoplasty. Commercially available posture analysis software was used to analyze the following variables: acromial horizontal alignment (AHA), angle between acromial and anterior superior iliac spines (A-AAIS), vertical alignment of right (R) and left (L) trunk (VAT), vertical alignment of R and L body (VAB) and horizontal alignment of R and L pelvis (HAP). Descriptive statistics and ANOVA for repeated measures were used, and effect sizes (ES) were measured; the level of significance was set at P<0.05. There were no significant differences in anthropometric variables among the assessments. Only HAP-R showed a significant decrease; however, when analyzed, ES, VAT- L and HAP- L in post60, and VAT-R, VAT-L, HAP-R, HAP-L and VAB-L in post90 showed large ES after mammoplasty (ES>0.70). There were significant reductions in pain at post60 and post90 in the neck, cervical spine, back, shoulder and arm (P<0.05). Following mammoplasty, an improvement in body posture, primarily in the alignment of shoulders, trunk and pelvis, and a decrease in pain in the upper limbs and spine, were observed.
An Anomalous Leg Flexor Muscle
Authors: Hughes Lowell A , Mahoney James L
Published: February 2017

LA Hughes, JL Mahoney. An anomalous leg flexor muscle. Can J Plast Surg 1993;1(1):50-51. A case of an anomalous flexor muscle in the leg (flexor digitorum intermedius) is described and the normal anatomy of the flexor digitorum longus discussed along with known variations and abnormal muscles in the deep posterior group of leg muscles.
Mirror Image Calcified Lesions of the Finger Tip: Two Case Reports
Authors: Waitzman Ariel A , Freiberg Arnis
Published: February 2017

AA Waitzman, a Freiberg. Mirror image calcified lesions of the finger tip: Two case reports. Can J Plast Surg 1993; 1 (1):52-54. Calcified lesions in the pulp of the finger tip are quite rare. Two case reports of mirror image lesions are presented with clinical, radiological and tissue pathology evaluation. All laboratory parameters were normal, there were no systemic signs or symptoms, and no evidence of crystal disease, neoplasm or previous trauma. These lesions may represent dystrophic calcification or tumoral calcinosis, but the etiology is far from clear. Excision and closure under local anesthesia was successful in managing these lesions.
Nipple and Areolar Reconstruction with Tattoo Pigments, Grafts and Local Flaps
Authors: Drever John M
Published: February 2017

JM Drever. Nipple and areolar reconstruction with tattoo pigments, grafts and local flaps. Can J Plast Surg 1993;1(2):84-90. In order to obtain symmetry when reconstructing the nipple and areola, the breast mounds are worked on first. Having reconstructed one side, the volume and shape of the opposite breast is modified as needed; then the areola can best be imitated on the reconstructed breast by placing tattoo pigments on the dermis of a thin skin graft. If the areola that is to be matched is light in colour, it is preferable to tattoo the skin directly. This is done as the initial procedure, as an improvement or as ‘maintenance’ to an already tattooed areola. The nipple reconstructed by grafting part of the opposite nipple or section of areola produces the most natural looking results. Another method involves lifting a tulip-shaped, centrally based dermis flap and then covering the areola and this flap with a thin skin graft with tattoo pigments smeared on its dermis. A nipple is made of the breast skin when the mound is revised by taking a segment off its lower quadrants.
Open Rhinoplasty – Should It Be the Procedure of Choice?
Authors: Neu Bernd R
Published: February 2017

BR Neu. Open rhinoplasty – Should it be the procedure of choice? Can J Plast Surg 1994;1(4):166-176. Open rhinoplasty is currently recognized for its usefulness in treating complex nasal deformities. This study examines and supports the routine use of the open approach for all cosmetic nasal operations. Forty consecutive open rhinoplasties were carried out. Included were primary, secondary and post-traumatic deformities. The surgical technique is described and the results are reviewed. Precision is enhanced with the open exposure. Alar cartilages are repositioned and contoured into shape with sutures. Tip rotation and elevation are more easily controlled. Cartilage grafts are used less often and, when required, are accurately sutured into place. A learning period is needed to understand the new perspective of the exposed cartilages and the effect on the external appearance. Asymmetries are easily created, and overcorrections must be avoided. The procedure takes longer. Nasal tip hypoesthesia and edema are more pronounced. The columellar scar is well accepted. The improved results with open rhinoplasty justify it becoming the procedure of choice in the author's practice. Minor modifications of the nasal dorsum or tip are still carried out through the endonasal approach.
Breast sensation following reduction mammaplasty
Authors: Fish Joel S , Bain James R , Levine Ronald
Published: February 2017

This study has quantitatively measured breast sensation following reduction mammaplasty using a vertical bipedicle technique. Breast sensation was quantitatively assessed by determining pressure and vibratory threshold values preoperatively in 20 subjects, and postoperatively in 15 patients. The nipple, areola and breast body were all independently assessed. Early results, less than one month postoperatively, revealed significant reductions in vibratory and pressure thresholds in the nipple and areola. Long term follow-up revealed that breast sensation returned to normal using this surgical technique.
Detection of Foreign Bodies using Ultrasound: A Possible Pitfall
Authors: Gan Bing Siang , Hurst Lawrence N , Evans H Brian , Downey Donal
Published: February 2017

Recently, a number of reports have brought the use of ultrasound scanning in the detection of foreign bodies to the field of hand surgery. A case is presented in which ultrasound was not able to diagnose the presence of a large (3.5 × 0.5 × 0.5 cm) nonradiopaque wooden foreign body lying between the flexor tendons of the forearm. However, embedded in ultrasound gel, the piece could readily be identified. This report serves as a reminder that the anatomical localization of a foreign body amid structures with vastly different echogenicity from its surroundings (such as flexor tendons of the hand and forearm) may reduce the usefulness of diagnostic ultrasound and that in such circumstances clinical suspicion may be a more reliable indication for exploratory surgery.
Invasive Group a Streptococcal Soft Tissue Infection and the Streptococcal Toxic Shock Like Syndrome
Authors: Fraulin Frankie Og , Giuffre Martin J , Campbell David D , Lobay Gary W , Edwards David C
Published: February 2017

A recent increase in the number of patients with severe group a streptococcal soft tissue infections and the streptococcal toxic shock like syndrome (stsls) in Edmonton sparked the interest to review eight cases that occurred between March 1991 and December 1993, including two patients after cosmetic surgery. These cases were felt to be sporadic and not linked. Four of the eight patients (age range 25 to 64 years), including one patient following upper blepharoplasties, developed invasive infection without shock. These patients presented one to seven days after the initiating event with only mild fever, but severe pain and localized erythema and swelling in the affected area which progressed quickly with the formation of bullae. Two streptococcal specimens were serotyped as M1 and contained streptococcal pyrogenic exotoxins (spe) a and B. Management included surgical debridement, penicillin, and clindamycin (interferes with M-protein and toxin production). All four patients recovered. The other four patients, including one patient following rhytidectomy, (age range 45 to 83 years) were much more ill and developed stsls. They rapidly developed septic shock within 12 to 24 h and progressed to multiorgan involvement despite surgical debridement. One streptococcal specimen was serotyped as M1 and positive for spe a and B, another specimen as M12 and positive for spe B, and another specimen as M-nontypable and positive for spe B. Two patients died within five days of presentation. The other two patients recovered following lengthy hospitalization, reconstructive surgery and rehabilitation.
Basal Cell Carcinoma of the Nose
Authors: Logarakis Nick F , Weinberg Michael J , Antonyshyn Oleh M , Forrest Christopher R , Assaad Dalal , Ackerman Ida
Published: February 2017

The goal of this study was to determine the demographic features, clinical presentation and treatment of basal cell carcinomas of the nose. To this end, a retrospective chart review of 229 patients, who presented to the Toronto Sunnybrook Regional Cancer Centre between January 1990 and January 1993, was conducted. There were 229 malignancies in 229 consecutive patients. Sixty-six percent of the patients were female and the overall mean age was 70 years. The ala was the most common site followed by the tip, lateral nose, dorsum, alar groove, root and columella. There were no cases of metastases. One hundred and two patients were treated with surgery and 101 patients received radiotherapy. The remainder were treated with electrodessication and curettage. Various methods of reconstruction were used and are discussed. This study demonstrates the various presentations of basal cell carcinoma of the nose and the usefulness and roles of a multidisciplinary team in its assessment and treatment.
Romance and tragedy of tuberculosis: Edward Archibald's contribution to the surgical treatment of pulmonary tuberculosis
Authors: Entin Martin A
Published: February 2017

Before streptomycin was discovered in 1945, outbreaks of tuberculosis (TB) were responsible for the destruction of the greatest number of people in history. During the 1960s, '70s and '80s, a continuous decline in the incidence of TB in the West created a feeling of complacency which led to the loss of vigilance and of clinical skill in diagnosing it; however, new outbreaks of TB have occurred in the last few years among aboriginals, drug addicts and patients with AIDS. Along with the rise of the incidence of the infection, the resistance of the TB bacilli to known antibiotics has reached alarming levels. Isolation and hospitalization of infected cases is being ordered in large North American cities; a careful search for contacts and close supervision for compliance during periods of treatment are imposed to avoid uncontrolled spread. The World Health Organization reports that a TB epidemic is sweeping through Eastern Europe as part of the global spread of AIDS. Thoracoplasty may have to be considered as a life saving measure for patients whose infection does not respond to any available antibiotic.
The use of pressure monitoring to standardize fetal arterial visualization
Authors: Shemshadi Hashem , Rohrich Rod J , Li Li , Robinson Jack B
Published: February 2017

The application of a new x-ray opaque postmortem perfusion system for the visualization of vascular structures in fetal models is presented. This new system allows pig fetus perfusion to be performed at pressures of less than 30 mmHg. At higher pressures, extravasations were observed in known weak spots in the fetal vasculature, and multiple perfusions at the same pressure exhibited similar patterns of extravasation (demonstrated at all pressures studied). Therefore this technique is controllable and predictable. It will allow determination of fetal vascular malformations which have been implicated as causes of many birth defects.
Managing the Infraorbital Sulcus of Ageing
Authors: Camirand André , Doucet Jocelyne , Harris June
Published: February 2017

The pathophysiology of the infraorbital sulcus is presented. A suggested technique to manage this consequence of ageing is to reposition the premalar fat pad properly by manipulating the superficial musculo-aponeurotic system. The result is a natural, youthful appearance.
Unusual Presentations of Ulnar Nerve Paresthesia: Mycotic Aneurysm and Leprosy
Authors: Moffatt Susan D , Parkhill Winston S
Published: February 2017

Ulnar nerve compression causing clinical symptoms is a common occurrence. There are numerous conditions that can cause compression. Recently two very interesting and unusual etiologies were seen at the Plastic Surgery service. Leprosy causing ulnar nerve compression is a rare occurrence in a Canadian hospital, and so is a case of palmar mycotic aneurysm in the postantibiotic era.
Extensive Odontogenic Keratocysts of the Maxilla: Review of the Literature and Report of Six Cases
Authors: Nish Iain A , Sándor George Kb , Weinberg Simon
Published: February 2017

The clinical, radiological and histological features of six large maxillary odontogenic keratocysts are reviewed. Special treatment considerations for extensive maxillary lesions are discussed. Patient follow-up, including imaging studies, is important to allow the early detection and treatment of recurrent lesions when they are small and well localized.
Donor Site Morbidity Following Free Tissue Transfer: A Preliminary Survey
Authors: Mahoney James , Kharaillah Eric , Drakos Dimitri
Published: February 2017

J Mahoney, E Kharaillah, D Drakos. Donor site morbidity following free tissue transfer: A preliminary survey. Can J Plast Surg 1998;6(2):85-88.

Donor site morbidity is becoming an important factor in the measurement of reconstructive success following free tissue transfer. A grading system based on five criteria (cosmesis, functional loss, wound healing, iatrogenic injury and pain) has been devised to evaluate and compare different donor sites in a uniform fashion. Questionnaires were sent to microsurgeons across Canada and to a series of patients asking them to report on their experiences with donor site morbidity. Completed questionnaires from 43 patients and 29 surgeons revealed that overall, donor site morbidity is low. This study represents a retrospective survey of the donor site of various free tissue transfers and highlights potential problems of several frequently used free flaps. The radial forearm flap had the highest morbidity, especially with regard to wound healing and cosmesis. Suggestions to improve studies in this area further are made.
Severe Soft Tissue Necrosis After Extravasation of Mitoxantrone: Case Report
Authors: Kara Mamood , Ross Douglas C
Published: February 2017

M Kara, DC Ross. Severe soft tissue necrosis after extravasation of mitoxantrone: Case report. Can J Plast Surg 1998;6(4):204-206. Subcutaneous extravasation of chemotherapeutic agents is a relatively common occurrence that is usually treated with non-operative techniques. An exception is injuries caused by doxorubicin (adriamycin), which can lead to progressive necrosis. We report a similar pattern of progression after extravasation of a newer agent – mitoxantrone. Wide excision and flap closure were required for wound healing. Mitoxantrone extravasation injuries require close monitoring and may produce full thickness necrosis followed by enlarging ulceration.
Empyema Necessitans Presenting As a Gas-Forming Cellulitis in An Hiv-Positive Man: Case Report
Authors: Dvali Linda , Quan Corinna , Pugash Robyn , Poulin Eric , Peters Walter
Published: February 2017

A 45-year-old human immunodeficiency virus (HIV)-positive male presented with massive gas-forming cellulitis of the chest wall and left arm, which developed one month after the onset of a Staphylococcus aureus pneumonia that was untreated. This condition was due to an empyema necessitans – an empyema that had drained through the chest wall to the soft tissues of the chest and left arm. Surgical debridement and long term intravenous antibiotic therapy successfully treated the condition.
Constant infusion schedule for adriamycin: a phase I-II clinical trial of a 30-day schedule by ambulatory pump delivery system.
Authors: Lokich J , Bothe A , Zipoli T , Green R , Sonneborn H , Paul S , Philips D
Published: February 2017

Eighteen patients received a continuous intravenous infusion of adriamycin for 14-60 days in a phase I study in which the dose rates were escalated from 2 mg/sq m/day to 5 mg/sq m/day to establish the optimal dose to be delivered over a 30-day period. The drug was delivered via a tunneled subclavian catheter by a portable infusion pump (Cormed model ML-6) primed to provide a volume of diluted drug of 10 cc/day. Leukopenia and stomatitis were observed at 4 mg/sq m/day doses or greater in 50% of courses. At doses less than 4 mg/sq m/day, only 3/17 courses (18%) were associated with stomatitis. Partial alopecia developed in all patients, but less than 50% of scalp hair was affected. The cumulative dose of continuous infusion adriamycin at 30 days is comparable to the dose delivered by standard bolus intermittent schedules (60-90 mg/sq m g 21 days), but the adverse drug effects are eliminated or substantially reduced. Cardiac toxicity was assessed in selected patients treated to 450 mg/sq m or greater by cardiac biopsy and/or gated pool studies. No histopathologic lesions were noted in 3 patients receiving 450 mg/sq m or greater. The recommended daily dose rate of adriamycin in this protracted infusion regimen is 3 mg/sq m/day. The phase II study of this schedule and dose rate in 38 additional patients (a total of 52 evaluable patients) demonstrated objective responses in 1/9 soft tissue sarcoma, 1/3 mesothelioma, 1/3 hepatoma, and 2/13 breast cancer. Phase III studies of the protracted continuous infusion schedule for adriamycin are indicated in that clinical activity is demonstrated at a substantial reduction in toxicity. Pharmacologic studies expanding the existing data base are also necessary.
Autologous bone-marrow transplantation: host effects of high-dose BCNU.
Authors: Takvorian T , Parker L M , Hochberg F H , Canellos G P
Published: February 2017

Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.
Phase II study of doxifluridine in advanced colorectal adenocarcinoma.
Authors: Abele R , Alberto P , Kaplan S , Siegenthaler P , Hofmann V , Ryssel H J , Hartmann D , Holdener E E , Cavalli F
Published: February 2017

Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer. The drug was given in a five consecutive day schedule by a bolus intravenous injection at a dose of 4 g/m2 per day and repeated every three to four weeks. Of 42 eligible patients, 40 had no previous chemotherapy. Response was defined in 27 patients having received two or more courses of doxifluridine. Seven responses (26%) were observed. Responses were seen only in sigmoid and rectum primary tumors. Toxicity consisted mainly of leukopenia (53% of the evaluable patients), nausea and vomiting (38%). Other toxicities such as dermatitis, myocardial injury, and hair loss were also observed. Doxifluridine has therapeutic activity, albeit limited, in advanced rectosigmoid adenocarcinoma.
Alteration of the pharmacokinetics of high-dose ara-C by its metabolite, high ara-U in patients with acute leukemia.
Authors: Capizzi R L , Yang J L , Cheng E , Bjornsson T , Sahasrabudhe D , Tan R S , Cheng Y C
Published: February 2017

The pharmacokinetics of high-dose cytosine arabinoside (HiDAC) given as a three-hour intravenous infusion at 3 g/m2 were studied in five patients with acute leukemia during relapse and/or remission of their disease. Apparent steady state plasma levels of ara-C during 13 infusions averaged 115 +/- 32 microM. Upon cessation of the infusion, cytosine arabinoside (ara-C) was rapidly cleared from the plasma. The apparent postinfusion kinetics of ara-C were triexponential with a distribution half-life of 16 minutes and elimination half-lives of 1.8 hours and six hours. Total clearance averaged 86 L per hour and mean residence time averaged 0.47 hours. Disease status (relapse or remission) had no apparent effect on the pharmacokinetic characteristics of ara-C. Peak levels of ara-U averaged 310 microM and the metabolite had an average apparent elimination half-life of 3.75 hours. Despite the persistence of ara-U at about 100 microM at the time of administration of subsequent infusions of ara-C, there was no further accumulation of ara-U in the plasma with repetitive infusions of HiDAC. In vitro studies indicate that ara-U can exert an inhibitory effect on deoxycytidine (dCyd) deaminase activity. The ratio of the Ki of ara-U to the Km of ara-C for cytidine (Cyd)-dCyd deaminase is 40:1; however, during the gamma phase of ara-C elimination, the ratio of ara-U:ara-C in plasma is at least 100:1. Thus, a retardation of systemic catabolism of ara-C by ara-U is possible. Two to three hours after the termination of the HiDAC infusion, the ara-C cerebrospinal fluid: plasma ratio is 1-3:1, a feature of potential therapeutic significance. The slower elimination of ara-C from the CSF may also contribute to the plasma gamma half-life.
Treatment of advanced breast cancer with mitomycin C combined with vinblastine or vindesine.
Authors: Garewal H S , Brooks R J , Jones S E , Miller T P
Published: February 2017

Mitomycin C together with either vindesine or vinblastine was given to 48 patients with previously treated advanced breast cancer. Thirteen (35%) of the 37 evaluable patients had a complete (one patient) or partial (12 patients) response. Overall median duration of response was 189 days (range, 90-700 days). Fifteen patients received mitomycin C and vindesine with six responses (40%) and a median response duration of 247 days (range, 162-700 days). Twenty-two patients received mitomycin C and vinblastine with seven responses (32%) and median response duration of 164 days (range, 90-330 days). Response duration for patients treated with mitomycin C plus vindesine was longer than that associated with mitomycin C plus vinblastine (p = 0.09). Significant toxicity included myelosuppression and neurologic symptoms, but was uncommon (less than 10% of patients). Therefore, the combination of mitomycin C and a vinca alkaloid appears to be useful in far-advanced refractory breast cancer.
Circulating immune complexes in childhood malignancies: a Pediatric Oncology Group study.
Authors: Castleberry R P , Duncan M R , Stagno S , Fernbach D J , Land V
Published: February 2017

Pretreatment serum samples obtained at diagnosis from 89 children with various pediatric malignancies were examined for circulating immune complexes (CIC) using the [125I]Clq binding assay. The study population consisted of 35 children with acute lymphocytic leukemia (ALL), 22 children with acute non-lymphocytic leukemia (ALL), 24 with neuroblastoma (NB), and eight with osteosarcoma (OS). Concomitant quantitation of immunoglobulins was performed in 55 patients, revealing normal values for age. Increased levels of CIC at diagnosis were found in 9%, 22%, 42%, and 50% of children with ALL, AML, NB, and OS, respectively. Except for a higher proportion of CIC-positive patients observed in stage IV NB (nine of 17) compared to stage I-III NB (one of seven), no correlation was observed between initial CIC level and presenting clinical features, response to treatment, prognosis, or presence of infection. Longitudinal sampling of six NB and two OS patients did not reveal a clear relationship between disease activity and quantity of CIC. For the pediatric malignancies studied, these data demonstrate minimal value in quantitating CIC as a means of assessing disease activity or predicting response to treatment and are in contrast to the apparently adverse effect of elevated pretreatment CIC on response to therapy and survival observed in adults with ALL, AML, and OS.
Second Central Nervous System Prophylaxis in Children With Acute Lymphoblastic Leukemia Who Relapse After Elective Cessation of Therapy
Authors: Rivera Gaston , George Stephen L. , Bowman W. Paul , Kalwinsky David , Ochs Judith , Dahl Gary V. , Hustu H. Omar , Simone Joseph V.
Published: February 2017

In the August issue of the Journal, the article by Rivera et al (1:471–476, 1983) contains an error. In Table 2 under the treatment for Phase II, the second complete line should read MTX† 10 mg/m2 + ara-C 50 mg/m2 IT every 6 wk.
The in vivo effect of thymic factor (thymostimulin) administration on circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease patients.
Authors: Velardi A , Spinozzi F , Rambotti P , Tabilio A , Losito A , Zampi I , Cernetti C , Martelli M F , Grignani F , Davis S
Published: February 2017

The in vivo effect of a calf thymus extract, thymostimulin, on the levels of circulating immune complexes (CIC) and serum lysozyme was evaluated in 32 patients with untreated Hodgkin's disease. Using the platelet aggregation test for detecting CICs, 12 patients (37%) had positive titers before thymostimulin treatment; 3 patients (10%) remained positive following therapy. Serum levels of Clq-binding immune complexes were evaluated (greater than 24.5 micrograms/ml) in 8 patients prior to thymostimulin therapy (mean value: 42.3 micrograms/ml); 3 patients continued to have elevated levels after treatment. Serum lysozyme levels for Hodgkin's patients was similar to control values (10.6 vs. 8.3 micrograms/ml); however, the Hodgkin's patients with initially elevated CICs had a lower serum lysozyme level than patients with initially normal CICs (12.9 vs. 7.3, p less than 0.02). Thymostimulin increased serum lysozyme levels in the Hodgkin's patients in whom the CICs were initially elevated (7.3 vs. 10.4 micrograms/ml, p less than 0.05). These data suggest that thymostimulin exerts an effect on the nonspecific immune system of Hodgkin's disease patients.
A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III).
Authors: Balch C M , Soong S J , Murad T M , Smith J W , Maddox W A , Durant J R
Published: February 2017

A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.
Intramedullary spinal cord metastases from small cell carcinoma of the lung.
Authors: Murphy K C , Feld R , Evans W K , Shepherd F A , Perrin R , Sima A A , Poon P Y
Published: February 2017

Four patients with intramedullary spinal cord metastases from small cell carcinoma of the lung (SCCL) are described, with emphasis on clinical presentation and treatment. All patients developed the Brown-Séquard syndrome due to intramedullary tumor in the cervical spinal cord, three within 2 mo after combined modality treatment using chemotherapy and radiotherapy. One patient presented with a Brown-Séquard syndrome and an extradural spinal cord compression from tumor. The radiological and cerebrospinal fluid findings are presented and discussed. Radiation treatment was administered to the involved segments of spinal cord in each patient. All patients responded; two for 3 and 7 mo, two for 3 and 4 wk, respectively. There was significant improvement in the quality of life for three of the four patients.
Chronic lymphocytic leukemia and other chronic lymphoid proliferations: surface marker phenotypes and clinical correlations.
Authors: Dillman R O , Beauregard J C , Lea J W , Green M R , Sobol R E , Royston I
Published: February 2017

A diagnosis of chronic lymphocytic leukemia (CLL) was made in 81 patients referred for peripheral blood lymphocyte typing (PBL). A retrospective review was undertaken to see if correlations existed between surface marker phenotype-determined subclasses and clinical features. Surface markers utilized were surface immunoglobulin (sIg), sheep erythrocyte receptor (E), 65,000-dalton human T lymphocyte antigen (T65), Ia antigen, and for sIg+ cells, heavy and light chains. All patients were Ia+. Cells of 70% of patients were sIg+ E- T65+ Ia+, and the clinical heterogeneity was that of classical CLL. Eight of the nine patients with sIg+ E- T65- Ia+ cells had a paraprotein. The sIg- E+ T65+ Ia+ phenotype represented classical T cell CLL. Three of the five patients in the sEg- E- T65+ Ia+ group had significant albuminuria, and two had nephrotic-range proteinuria. Use of additional monoclonal antibodies to B cell surface antigens should further subclassify CLL and other lymphoproliferative disorders. Interesting clinical correlations with certain phenotypic subclasses do exist, and further subclassification and long-term follow-up may yield correlations between phenotypes and prognosis.
Methotrexate-induced renal impairment: clinical studies and rescue from systemic toxicity with high-dose leucovorin and thymidine.
Authors: Abelson H T , Fosburg M T , Beardsley G P , Goorin A M , Gorka C , Link M , Link D
Published: February 2017

Four separate groups of patients have been studied: (1) The effect of high-dose methotrexate (MTX) administration on glomerular filtration rate was determined by pre- and posttreatment inulin and creatinine clearances in nine patients. Measurements were made prior to and 24-40 hr after drug administration. Inulin and creatinine clearances both decreased a mean of 43%. No signs of systemic toxicity occurred. (2) Three other patients given high-dose courses of MTX developed MTX toxicity. Their creatinine clearance decreased an average of 61%. (3) In a separate group of five patients undergoing weekly MTX treatment, comparison of serum MTX pharmacokinetics with and without alkalinization of the urine demonstrated no significant difference in peak serum MTX levels or serum MTX decay. (4) Eight additional patients with severe renal dysfunction secondary to MTX were treated with increased doses of leucovorin and a continuous infusion of thymidine (8 g/m2/day) once renal failure was recognized. When high-dose leucovorin and thymidine were begun 48-72 hr after the MTX infusion, severe toxicity in the form of leukopenia, thrombocytopenia, diffuse mucositis, stomatitis, or skin rash was averted. We concluded the following: (1) high-dose MTX causes a subclinical decrease in glomerular filtration rate with each administration, even in nontoxic courses; (2) alkalinization of the urine with sodium bicarbonate does not alter plasma MTX decay, while volume expansion (hydration) is maintained constant; and (3) rigorous monitoring of serum creatinine and serum MTX levels 24-48 hr after MTX administration allows for the institution of rescue measures, including leucovorin and thymidine, which will abort the systemic toxicity that accompanies MTX-induced renal failure.
Combination chemotherapy with cis-diamminedichloroplatinum and vinblastine in advanced non-small cell lung cancer.
Authors: Woodcock T M , Blumenreich M S , Richman S P , Kubota T T , Gentile P S , Allegra J C
Published: February 2017

Twenty-seven patients (25 males and 2 females) with histologically confirmed, unresectable, or metastatic non-small cell lung cancer were entered on a combination chemotherapy protocol including cisplatinum and vinblastine sulfate (DDP)(VLB). Patients had to have measurable disease as defined by the presence of two clearly measurable perpendicular diameters, be untreated with either chemotherapy or radiation therapy, and give informed consent to be eligible for study entry. The median age was 57 yr and the median performance status was 70 (Karnofsky scale); 10 patients had epidermoid carcinoma, 9 adenocarcinoma, 4 large cell carcinoma, and 4 undifferentiated carcinoma. All patients had intrathoracic disease, 12 also had extrathoracic lymph node involvement, 8 bone involvement, 2 liver metastasis, and 2 central nervous system metastasis prior to beginning chemotherapy; 9 patients had involvement of one site, 12 of two sites, 5 of three sites, and 1 of four sites. Cisplatinum was given as a short intravenous infusion of 120 mg/m2 on days 1 and 28, and then every 6 wk. Vinblastine was administered as an intravenous injection of 8 mg/m2 on days 1, 14, and 28, and then every 3 wk. Patients were evaluated prior to each course of cisplatinum. If progression occurred, therapy was discontinued. If stabilization or response was noted, then therapy was continued until intolerable toxicity or progression supervened. Every patient entered is considered evaluable for toxicity and response. There were no complete remissions; 14 patients achieved a partial response, 3 had a minimal response, 5 had stabilization of their disease, 1 had disease progression, and 4 are considered to have had drug deaths. Responses were seen after the first cisplatinum course in 13 patients and after the second in 1. Toxicities seen were universal nausea and vomiting; elevation of creatinine occurred in 6 patients, ranging from 2.1 to 14.6 mg/dl, and was clinically significant in 2 patients. Myelosuppression, with a leukocyte nadir of less than 3.0 X 10(9)l in 10 cases and platelet nadir of less than 100.0 X 10(9)l was seen in 5 cases and partial hearing deficit occurred in 2 patients. Median survival was 22 wk for the whole group (24 wk for the whole group if the 4 early drug deaths are excluded). Median survival was 26 wk for responding patients and 13 wk for nonresponding patients (remains the same if the early deaths are excluded from the latter group).(ABSTRACT TRUNCATED AT 400 WORDS)
Osteogenic sarcoma: alterations in the pattern of pulmonary metastases with adjuvant chemotherapy.
Authors: Jaffe N , Smith E , Abelson H T , Frei E
Published: February 2017

The number and time to appearance of pulmonary metastases were evaluated in 15 patients with osteogenic sarcoma receiving adjuvant chemotherapy with high-dose methotrexate and doxorubicin (adjuvant group). The results were compared to 33 age- and sex-matched controls (control group). The adjuvant group demonstrated a reduction in the number and a delay in the appearance of the metastases. The median time to development of metastases was 17 mo in the adjuvant group and 7 mo in the control group, and the median number of metastases was 2 and 12, respectively.
Comparison of extramedullary plasmacytomas with solitary and multiple plasma cell tumors of bone.
Authors: Knowling M A , Harwood A R , Bergsagel D E
Published: February 2017

Patients with solitary osseous plasmacytomas (SOP) differ from those with extramedullary plasmacytomas (EMP) in that they are younger and the proportion of males is smaller. The median survival of the two groups is similar: 86.4 mo for SOP, and 100.8 mo for EMP. Progression-free survival, however, is much better for EMP. Only five EMP patients have progressed following initial radiation therapy: one developed a single bony lesion, two progressed to multiple myeloma, and two developed multiple EMP. Thus, 71% of EMP patients are progression free at 10 yr, and most deaths do not result from plasma cell neoplasia. In contrast, 13 SOP patients have progressed to develop additional osteolytic lesions, so that only 16% of SOP patients are progression free at 10 yr; death resulted from progression to multiple myeloma in most of these patients. In EMP patients the occurrence of involved lymph nodes at the time of diagnosis in seven, and initial relapse in regional nodes in three, suggest that consideration should be given to including regional lymph nodes in the radiation fields used to treat these patients.