Laparoscopic exploration for the clinically undetected hernia in infancy and childhood.

BACKGROUND: Routine contralateral groin exploration in infants and children with a clinically detected inguinal hernia is the subject of much debate. The detection of a patent processus vaginalis by transinguinal laparoscopy has proven advantageous. However, controversy remains regarding the true incidence of a contralateral patent processus vaginalis as well as which of these will actually develop into a clinically apparent hernia. METHODS: From January 1997 through December 1999, 358 infants and children (aged 1 to 157 months, mean 32) were treated in the three University of Oklahoma teaching hospitals in Tulsa, Oklahoma, for inguinal hernia. The findings at laparoscopic exploration of the contralateral side were recorded to determine the incidence of contralateral patency as it relates to a child's age, gender, and side of the initial clinical diagnosis. RESULTS: The overall incidence of a patent processus vaginalis on contralateral examination was 33% (117 of 358). All patent processus vaginalis were repaired. Bilateral inguinal hernia was significantly more common in younger patients (present in 50% if less than 1 year, 45% if less than 2 years, 37% if less than 5 years, and 15% if greater than 5 years of age; P <0.05). In boys, the incidence was 49%, 45%, and 32% in those under 1 year of age, under 2 years of age, and in total, respectively. In girls, the incidence was 59%, 50%, and 37% in those under 1 year of age, under 2 years of age, and in total, respectively. The side of the clinically detected hernia did not influence the laparoscopic findings of a contralateral hernia with 30% (50 of 169) positive findings on left inguinal exploration versus 31% (28 of 90) positive findings on right inguinal exploration. CONCLUSIONS: The high incidence of a contralateral patent processus vaginalis warrants routine laparoscopic exploration in infants and children undergoing unilateral inguinal hernia repair, especially those less than 5 years of age. The use of transinguinal laparoscopic explorations avoids unnecessary open exploration in 66% of infants and children undergoing inguinal hernia repair.

Adjuvant radiation after modified radical mastectomy for breast cancer fails to prolong survival.

Recent literature has reported improved local disease control and overall survival in premenopausal node-positive (stage II, and III) breast cancer patients undergoing modified radical mastectomy (MRM) using radiation therapy (RT) combined with chemotherapy. To assess the efficacy of postoperative RT in our own community, we analyzed all patients undergoing MRM for carcinoma utilizing an extensive database from the three major teaching hospitals in Tulsa, OK, between 1965 and 1993. A total of 5257 patients underwent MRM during this time period. One hundred thirty-seven patients were excluded for insufficient data or because they were found to be at stage IV, leaving a total study population of 5125. Overall survival (OS), overall mean survival (MS), disease-free survival (DFS), and locoregional DFS (LRDFS) were analyzed for all patients and were further analyzed according to stage, lymph node involvement, and menopausal status. Median follow-up was 103 months. Statistical analysis was performed using Kaplan-Meier and t-tests. The DFS at 10 years was 65 per cent in the RT group and 80 per cent in the patients who did not receive RT (P = 0.00). No improved DFS was obtained in the radiation-treated patients, regardless of stage, lymph node involvement, or menopausal status. Similarly, the LRDFS at 10 years was 91 per cent in the RT group and 96 per cent in the patients who did not receive RT (P = 0.00). No improved LRDFS was obtained in the radiation-treated patients, regardless of stage, lymph node involvement, or menopausal status. The overall MS was 97 months in the RT group and 104 months in the patients who did not receive RT (P = 0.00). Comparisons of overall MS rates revealed apparent survival benefits from RT in the premenopausal node-negative group, postmenopausal one to four-positive-node group, and all stage I patients. This apparent survival advantage was not confirmed by Kaplan-Meier curves of OS. No other overall MS differences were detected according to stage, lymph node, or menopausal status. Using Kaplan-Meier survival curves, the OS in the RT group at 10 years was 46 per cent, and 63 per cent in the patients who did not receive RT (P = 0.00). No improved OS was obtained in the radiation-treated patients, regardless of stage, lymph node involvement, or menopausal status. These findings from a large breast cancer database failed to demonstrate any meaningful benefit from RT after MRM and serve to further question the efficacy of this treatment modality in postmastectomy breast cancer patients.

Phyllodes tumors of the breast: a review of 32 cases.

Most general surgeons involved in breast cancer care have limited experience with phyllodes tumors. We analyzed a comprehensive database incorporating 8567 breast cancer cases treated surgically in the Tulsa, Oklahoma, region between 1969 and 1993. This yielded 32 cases of phyllodes tumors (0.37%) in 31 patients. The median age was 57 years (range, 18-91). There were 9 low-grade (28%), 2 intermediate-grade (6%), and 21 high-grade (66%) lesions. Size distribution consisted of 23 (72%) lesions 5 cm or less and 9 (28%) greater than 5 cm (mean, 3; range, 1.2-17.5 cm). Of 137 resected nodes in 13 patients, none were positive for metastatic disease. Surgical management consisted of wide excision or mastectomy. No patients received adjuvant chemoradiation therapy. The disease-free, locoregional disease-free, and overall mean survival rates were 80, 81, and 97 months, respectively. Ten-year disease-free survival (DFS), locoregional disease-free survival (LRDFS), and overall survival (OS) rates were 66, 72, and 55 per cent, respectively. Although there was a tendency toward a higher rate of locoregional recurrences and metastases with high-grade lesions, this was not statistically significant and did not affect DFS, LRDFS, or OS rates. Similarly, size of lesion did not affect DFS, LRDFS, or OS rates. Three patients (9.6%) had metastatic disease at presentation, and a further two (6.4%) developed metastases during follow-up. Overall, nine (28.1%) recurrences developed in eight patients, seven locoregional and two distant. Four patients (12.9%) died with evidence of disease. These findings indicate prolonged survival in this patient population with cystosarcoma phyllodes. Wide local excision of primary and recurrent lesions remains the mainstay of therapy. Neither regional lymph node dissection nor adjuvant chemoradiation adds significant benefit.

Melanoma vaccines as a therapeutic option.

BACKGROUND: In 1998, 41,600 new cases of melanoma with 7,300 deaths were expected. Worldwide, the incidence has risen 5% a year against a backdrop of generally decreasing cancer trends. Later stages of melanoma carry a severe prognosis. The need for newer, more effective therapeutic strategies for cancer is obvious. For melanoma, early diagnosis and surgical treatment are the only options that are currently curative. Chemotherapy and radiation therapy are of limited efficacy. METHODS: We reviewed the various forms of immunotherapy, concentrating on vaccine therapy. We then reviewed the history of our own vaccine in the context of the field of immunotherapy, and compared efficacy, immune response, production methods, and survival. RESULTS: Survival is improved among recipients of melanoma vaccine when compared with patients receiving conventional therapy. CONCLUSIONS: Imnmunotherapy in the form of melanoma vaccines is better than conventional therapy and is trending toward purer antigenic preparations.

Incidence of fetal alcohol syndrome in northeastern Manitoba.

The incidence of fetal alcohol syndrome (FAS) in northeastern Manitoba was investigated by examining all 745 live births occurring in Thompson General Hospital in 1994. Birth records were screened with criteria designed to capture all potential FAS cases. Cases were then eliminated if follow-up records indicated the child was not developmentally delayed or no longer had the small head or body size identified at birth. Cases still meeting criteria were personally examined. Five cases of FAS were identified among the 46% of eligible children screened at age 2, roughly an incidence of 7.2/1,000. However, because only 46% of the high risk cases were personally examined, incidence could be as high as 14.8/1,000. Only 1/5 FAS cases had been identified prior to our investigation. The results indicate the incidence of FAS in northeastern Manitoba is very high and that much greater effort needs to be made in its prevention and early detection.

Squamous cell carcinoma of the breast following silicone injection of the breasts.

During the 1960s, injecting liquid silicone into the breasts for augmentation purposes was a common practice. Many women suffered complications, usually developing silicone mastopathy, but there have been reports of carcinoma as well. A case of squamous cell carcinoma of the breast is reported in a patient who had previously undergone injection of silicone into the breasts. Upon review of the literature, this is only the second reported case of squamous cell carcinoma of the breast following silicone injection. Squamous cell carcinoma of the breast is a very rare tumor comprising 0.04 to 0.075 percent of all breast malignancies. The tumor appears to develop from metaplasia of benign epithelial cells within the breast. Many theories are presented for the development of this metaplastic process. The clinical presentation, evaluation, and treatment of squamous cell carcinoma of the breast is quite similar to that of infiltrating ductal carcinoma of the breast of comparable stage and size.

Comparison of melanoma antigens in whole tumor vaccine to those from IIB-MEL-J cells.

Immunotherapy for melanoma shows promise. Our previous whole tumor (WT) vaccine was noted to have positive clinical effects. We have now developed a new, safer melanoma vaccine that is derived from IIB-MEL-J tissue culture (TC) cells. In this study, we compare by Western blot analyses the antigens in the WT vaccine to antigens in the TC vaccine. Sera from 12 WT vaccine recipients, 8 melanoma patients who received no immunotherapy, and 8 controls served as a source of antibodies to investigate potential antigens in the vaccines. Three major antigenic peptides with approximate molecular weighs of 46, 40, and 36 kDA were present in both vaccines, while two other antigenic peptides with approximate molecular weighs of 68 and 48 kDA were present only in the TC vaccine. The reaction was similar between the patients who received the WT vaccine and those who did not receive the vaccine. Some of the individuals who did not have melanoma showed some reaction, but not to the extent of the melanoma patients. The intensity of immunostaining was greater for the TC vaccine when compared to the WT vaccine, indicating that these proteins are in a higher concentration in the TC vaccine. This new vaccine from IIB-MEL-J tissue culture cells provides a higher yield and a much more consistent source of potentially clinically relevant antigens without risk of infection or contamination by other irrelevant materials.

The relationship between concentrations of proinflammatory cytokines within gingiva and the adjacent sulcular depth.

The objective of this study was to determine and compare concentrations and ratios of 3 proinflammatory cytokines, interleukin (IL) IL-1beta, IL-6, and IL-8 within gingival tissue biopsies adjacent to < or = 3, 4 to 6, or >6 mm sulci. All gingiva adjacent to > or = 4 mm sulci had clinical evidence of active inflammation. Factorial analysis of variance suggested significant effects of sulcus depth on the type and concentration of the three cytokines in the adjacent gingiva (P < 0.001). IL-8 concentrations were highest in gingiva adjacent to < or = 3 and lowest adjacent to >6 mm sulci (P < 0.001). In contrast, IL-6 concentrations were lowest in gingiva adjacent to < or = 6 mm and highest adjacent to >6 mm sites. IL-1beta concentrations were highest in gingiva adjacent to >6 mm and lowest adjacent to 4 to 6 mm sites; they were also higher adjacent to < or = 3 mm than adjacent to 4 to 6 mm sites (P < 0.01). Multiple regression analysis suggested that sulcular depth, type of cytokine, and cytokine concentration were significantly correlated (P < 0.001). Ratios of gingival cytokines changed with increased sulcular depth. In gingiva adjacent to < or = 6 mm sites, IL-8 was the most and IL-6 the least prevalent. In gingiva adjacent to > or = 6 mm sites, IL-8 was the least and IL-1-beta the most prevalent. The data suggest that the characteristics of the gingival cytokine network are affected by adjacent sulcular depth. These data could be used to design adjunct diagnostic tests for progression of periodontal diseases.

Longitudinal cholecystectomy study: patterns of care in a total community experience.

The purpose of this study was to determine outcomes and safety of laparoscopic cholecystectomy (LC) versus open cholecystectomy (OC) in a community setting at multiple open staff hospitals with multiple surgeons. This second-year study retrospectively examined all cholecystectomy records in one city at each of five hospitals over a 1-year period beginning in April 1991 through March 1992. All charts were examined for type of surgery, rate of conversion to open procedure, sex, weight, previous abdominal surgery, surgeon, hospital, preoperative workup, operative time, antibiotic prophylaxis, cholangiograms, concurrent procedures, drains, hospital stay, common duct stones and their follow-up, pathology, reoperations, complications, and mortality. One thousand eight hundred one gallbladders were removed. One thousand three hundred four (72.4%) were successfully removed at LC. One hundred eighty-three (10.2%) others were attempted laparoscopically and converted to open cholecystectomy (CC), which represented 12.3% of the attempted LCs. Three hundred fourteen (17.4%) were removed via a standard OC. The mean operative times were 72.3 minutes for LC, 100.1 minutes for CC, and 86.2 minutes for OC. Cholangiography was attempted in 916 (70.3%) LCs, 144 (78.7%) CCs, and 250 (79.6%) OCs, with similar operative times, except in LC, when done via the GB, operative time was 65.2 versus 73.4 minutes when done via the cystic duct. Diagnosis of acute cholecystitis occurred in 306 (23.5%) LCs, 119 (65.0%) CCs, and 145 (46.2%) OCs. Complications requiring reoperation occurred in 30 (2.3%) LCs, 5 (2.7%) CCs, and 5 (1.6%) OCs. Common bile duct (CBD) injuries occurred in 5 (34%) LCs, with 4 converted to CC and 1 repaired 5 days later. Trocar site hernias occurred in 11 (0.8%) LCs. Thirty-nine surgeons participated in the study with mean numbers of 33.4 LC cases, 5.5 CC cases, and 7.2 OC cases, with ranges of 1 to 165 LC cases, 1 to 17 CC cases, and 1 to 24 OC cases. Death occurred in 12 (0.9%) LC cases, 4 (2.2%) CC cases, and 25 (8.0%) OC cases. The mean hospital stay was 39.6 hours for LC, 156.5 hours for CC, and 198.3 hours for OC.

Fluorescence and site-directed mutagenesis studies of interleukin 1 beta.

The authors mutated two key residues in the sequence of the cytokine interleukin 1 beta, namely the double mutant Phe46 to Trp46 and Trp120 to Phe120 and the single point mutation Lys103 to Leu103 and measured the resulting receptor binding and biological activities. The biological and receptor binding activities of the Trp46 mutein was reduced by a factor of 12 and 25, respectively, and surprisingly, those of the Leu103 mutein, 2600 and 600-fold relative to the wild-type protein. The authors had previously showed that Lys103 was unusually reactive to a variety of derivatizing agents. Furthermore, the Trp to Phe mutation allowed us to monitor the local environment of that residue by studying its intrinsic fluorescence properties, as well as any change in the fluorescence properties of Trp120 of the Leu103 mutein. The results of these studies show that mutation of Lys103 to Leu103 produces subtle long-range changes in the micro-environment of Trp120, indicative of a key role for this residue in the folding of the entire protein.

The value of axillary dissection in T1a breast cancer.

BACKGROUND: Some authors have stated the undesirability of axillary lymph node dissections for very small breast cancers, because so few of their patients have lymph node metastases (3% for T1a lesions in one series). METHODS: Of 6,308 breast cancer cases reviewed from three large urban hospitals 3,077 single primary cases with both axillary dissection and accurate tumor measurements were statistically analyzed. RESULTS: For T1a lesions we found axillary metastases to be four times higher (12%) than others have reported. For each tumor size there was a statistically significant difference in the percentage of axillary metastases. There was also a statistically significant difference in the breast cancer-specific survival of patients with different tumor sizes (n = 3,077) at the 3-year, 5-year, 7-year, and 10-year periods. CONCLUSION: These results justify axillary node dissections even for very small invasive cancers of the breast, particularly for invasive ductal histology.

Effects of the adjuvant MPL + TDM on tumor challenge in the B16 mouse melanoma model.

Mice were injected three times at 2 week intervals with the adjuvant MPL + TDM or phosphate-buffered saline. Two weeks after the last injection, all mice were challenged subcutaneously with a tumorgenic dose of B16 tumor and observed for 40 days. The adjuvant hastened the time at which tumors appeared (P = 0.02).

Surgical treatment of cancer of the pancreas in large community hospitals.

A retrospective study compares the success rates of surgical treatment of cancer of the pancreas in large community hospitals. Although none of the surgeons averaged as many as two pancreaticoduodenal resections per year for the period of this study, their results compared well with other published series except for a few centers and surgeons who did a very high volume of such resections. Results of the study indicate that well trained surgeons in well staffed and well equipped community hospitals can provide acceptable results in pancreaticoduodenectomies for cancer of the pancreas.

Five-year survival in breast cancer treated with adjuvant immunotherapy.

In this follow-up report of the treatment of primary breast cancer with adjuvant immunotherapy, a total of 95 patients were studied: 46 patients with stage I breast cancer and 49 patients with stage II breast cancer. All patients underwent standard surgical treatment and received immunotherapy as adjuvant treatment. Patients received a primary series of eight doses (1 mL of tumor-associated antigen preparation given as 0.2 mL intradermally and 0.8 mL subcutaneously) given over 8 weeks, and then booster injections every 3 months for at least 2 years. The 5-year survival with adjuvant immunotherapy was 83% for those with negative axillary nodes and 53% for those with positive nodes; this compares favorably with national 5-year survival statistics from two other studies (node-negative, 72% and 83%; node-positive, 51% and 59%). Based on these data, the addition of immunotherapy to other adjuvant therapies in randomized prospective trials seems both reasonable and justified.

Laparoscopic cholecystectomy: an initial community experience.

The initial 950 consecutive laparoscopic cholecystectomies performed in one city at four hospitals by 30 general surgeons are reported, covering a period from April 4, 1990 to April 3, 1991. There were two operative deaths (0.2%), three common bile duct lacerations (0.3%), two subhepatic abscesses, two bowel perforations, and three bile leaks, two requiring laparotomy. Seven episodes of bleeding occurred, of which five required laparotomy, but none involved a major vessel. Sixty-five procedures were converted to open (6.7%). The mean operative time was 85.4 min. Intraoperative cholangiography was adequately completed in 49.8% and not attempted in 30.3%. Thirteen patients (2.7%) were found to have common duct stones. The pathologic diagnoses were chronic cholecystitis in 784 patients (82.5%), acute cholecystitis in 145 (15.3%), and cancer of the gallbladder in one (0.1%). Hospital stays ranged from 4 h to 31 days (mean 49.5 h). This procedure can be learned and performed safely in a community setting.

Thermal profiles of electrocauteries, the Nd:YAG laser, and the electromagnetic-field focusing system.

Electromagnetic-field focusing (EFF) is a method of converging induced eddy current onto a pointed tip of a tuned length return circuit in the near field of a resonator, which results in the production of high temperature. Previously reported applications of this method include various devices for local hyperthermia and a precision surgical device. The latter is currently being used in human clinical trials under two investigational device exemptions from the Food and Drug Administration. In the present work, the thermal profile produced in a uniform, tissue-simulating phantom by the hand-held probe of the surgical EFF system is compared with those produced by mono- and bipolar electrocauteries and by a contact Nd:YAG laser. At the equivalent power setting and 2-cm insertion depth, the EFF probe was shown to have a tighter thermal profile than the monopolar electrocautery or the contact Nd:YAG laser. This finding is consistent with earlier histologic evidence that brain cortical tissue cut by the surgical EFF probe had minimal thermal damage in the tissue surrounding the incision.

Bacteriophage phi X-174 as an aerobiological marker for surgical plume generated by the electromagnetic field focusing system.

The aerosol of surgical plume could be measured effectively with the use of bacteriophage phi X-174 as a biological marker, in contrast to previous methodologies reported by others. Recovery of virus plaque-forming units was highest from hydrophobic polytetrafluoro-ethylene membranes compared to hydrophobic polycarbonate screen filters or polyvinylidene difluoride depth filters, indicating that the method of virus recovery strongly affects the utility of a virus as an aerobiological marker. With this new method, surgical plume was indeed found in significant amounts when cutting tissue phantoms made with agar containing virus. The Electromagnetic Field Focusing System was used, which is a new thermal surgical device. The nominal power setting did not appear to be a factor in the amount of virus recovered. However, when pulse modulating the power by adjusting the crest factor from 1.4 to 4.3, a measure of the duty cycle for power delivery which adjusted the device from its cutting to haemostatic mode, a nearly five-fold increase in surgical plume, as evidence by the recovery of phi X-174 plaque forming units, was seen. The data indicate that bacteriophage phi X-174 can be used effectively as an aerobiological marker for aerosols generated during clinical procedures, and reinforce the need to use a safety vacuum during aerosol generating procedures. The availability of a safe and economical biological marker for aerosols from clinical procedures, which may lead to acquired infections in hospital personnel, makes evaluation of procedures and containment systems markedly easier. The data also indicates that surgical plume biohazard may be present in other techniques that employ pulse modulation including surgical lasers and electrocauteries.

Use of a Marlex fan in the repair of direct and indirect hernias by laparoscopy.

Sixty-seven laparoscopic hernia repairs are described with the use of Marlex mesh in a new fan configuration in 56 cases. This fan is easily constructed and manipulated endoscopically. It offers more surface area of Marlex to the surrounding tissues and occupies more potential space, being conformable to the space left by a hernia sac. In 67 repairs we have had one recurrence at a maximum of 10 months follow-up. One patient had contralateral lower extremity deep venous thrombosis (DVT), one had a palpable inguinal mass, and two patients suffered temporary orchialgia.

Melanoma tumor vaccine: five-year follow-up.

For many years, various melanoma vaccines have been employed. This is a unique melanoma vaccine in that it is a subcellular tumor homogenate and no adjuvants have been added. This vaccine has been given to 129 stage I and 61 stage II melanoma patients. All were followed at least 5 years and had 87.5% and 63.9% 5-year survival rates, respectively. Sixty-four stage I males and 65 stage I females had 84% and 90% 5-year survival rates, respectively. We saw no difference between those with or without lymph node dissection. Thirty-six stage II males and 25 stage II females had 66.7% and 60% 5-year survival rates, respectively. Of stage II patients, 23 had only one positive node, 22 had two to four positive nodes, and 9 had five or more positive nodes with 69%, 63%, and 55% 5-year survival rates, respectively. Large published series were used as historical controls [6,27,28], and significant differences were noted when compared to our stage II patients (P = 0.001)--those with two to four positive nodes (P = 0.03), and those with five or more positive nodes (P = 0.04). We conclude that there is a significant increase in survival for these stage II patients, at high risk of recurrence, receiving a tumor homogenate vaccine. This vaccine warrants further analysis, development, and use in a phase III randomized clinical trial.

Immunotherapy for malignant melanoma: a review and update.

Several different approaches to the application of specific active immunotherapy for the adjuvant therapy of melanoma have developed independently. Specific active immunotherapy refers to autologous or allogenic inoculation or transplantation of tumor cells or cell products into patients with cancer. Several different types of tumor vaccines have been studied and have been combined with different immunotherapeutic modalities. This report will include a review of several of those different techniques and will also review the observed 5-year survival rates for a melanoma tumor homogenate (concentrated) vaccine, developed by L.J. Humphrey and colleagues.