Role of differential neuroaxial blockade in the evaluation and management of pain in chronic pancreatitis.

OBJECTIVES: Chronic pancreatic pain is difficult to treat. Surgical and medical therapies directed at reducing pain have met with little long-term success. In addition, there are no reliable predictors of response including pancreatic duct diameter. A differential neuroaxial blockade allows characterization of chronic abdominal pain into visceral and nonvisceral pain origins and may be useful as a guide to the treatment. Pain from an inflamed, and scarred pancreas should be visceral in origin. The purpose of our study was to determine the frequency with which patients with chronic pancreatitis have visceral pain and whether our modified differential neuroaxial blockade technique using thoracic epidural analgesia can accurately predict which patients will respond to medical or surgical therapy. METHODS: We retrospectively reviewed the medical records of patients with a firmly established diagnosis of chronic pancreatitis (Cambridge classification, calcifications) who had undergone a differential neuroaxial block for their chronic abdominal pain evaluation. Patient demographics and medical or surgical treatment for pancreatic pain was recorded. Response to therapy was defined by a 50% reduction in pain by verbal response score. RESULTS: A total of 23 patients were identified. Alcohol was the most common etiology for chronic pancreatitis (15 of 23, 55%). Surprisingly, the majority of chronic pancreatitis patients had nonvisceral pain (18 of 23, 78%) and only 22% (5 of 23) had visceral pain by differential neuroaxial block. Four of five patients (80%) with visceral pain responded to therapy, whereas only 5 of 17 (29%) of patients with nonvisceral pain responded. CONCLUSIONS: Surprisingly, patients with chronic pancreatitis commonly have nonvisceral pain. Differential neuroaxial blockade can predict which patients will respond to therapy.

Dynamic laryngotracheal closure for aspiration: a preliminary report.

OBJECTIVES/HYPOTHESIS: An estimated 500,000 patients per year in the United States. are affected by stroke-related dysphagia. Approximately half experience aspiration, which can lead to pneumonia or death. Aspiration may result from many factors, including delayed transport of the bolus, faulty laryngeal elevation, and poor coordination or inappropriate timing of vocal cord closure. Interventions carried out to protect the lungs are usually irreversible, destructive to the upper airway, and rarely prevent the need for enteral tube feeding. STUDY DESIGN: We present a report of the first implantations of a new device in an FDA-approved study to restore dynamic laryngotracheal separation. Two stroke patients needing tracheostomy were selected based on chronic aspiration verified by clinical and radiologic criteria (modified barium swallow [MBS]). METHODS: The left recurrent laryngeal nerve was exposed and electrically stimulated to verify vocal fold adduction. Huntington Medical Research Institute Bipolar Helical Electrodes were then implanted around the nerve. The leads were tunneled and linked to a NeuroControl Implantable Receiver-Stimulator placed subcutaneously on the chest wall. Activation of the stimulator was performed through an external transmitter linked by induction. RESULTS: The device was successfully triggered intra- and postoperatively. Serial flexible fiberoptic endoscopies and MBS demonstrate that aspiration is systematically arrested using low levels of electrical stimulation (42 Hz, 48-100 microsec, 1 mA). DISCUSSION: This pioneering work has shown that aspiration can be controlled without airway damage for a wide population of neurologically impaired patients because it appears more physiological than standard therapies. CONCLUSION: Based on the first two patients, paced laryngotracheal separation is clinically effective in controlling aspiration.

Role of angiography and embolization for massive gastroduodenal hemorrhage.

The role of mesenteric angiography and embolization for massive gastroduodenal bleeding is unclear. We reviewed the records of patients who underwent angiography for acute, nonmalignant, and nonvariceal gastric or duodenal hemorrhage that was documented but not controlled by endoscopy. Fifty patients were identified over a 7-year period ending in March 1998. Only 17 patients (34%) were originally admitted to the hospital with gastrointestinal bleeding. All required treatment in the intensive care unit (mean 15 days) with a mean APACHE III score of 79 (29% predicted hospital mortality), and 32 (64%) had organ failure. A mean of 2.1 endoscopies were performed to locate the source of acute duodenal bleeding in 37 (74%) and gastric bleeding in 13 (26%). An average of 24.3 units of packed red blood cells were transfused per patient. Twenty-five patients (50%) were found to have active bleeding at angiography; all were treated by embolization as were 22 who underwent empiric embolization. Twenty-six patients (52%) were successfully treated by embolization and thus spared imminent surgery. Multiple variables were compared between those who were successfully treated by embolization and those considered failures. Time to angiography was considerably shorter (2.5 vs. 5.8 days, P<0. 017) and fewer total units of packed red blood cells were used (14.6 vs. 34, P<0.003) in those who were successfully treated. There was also a strong trend toward using fewer units of packed red blood cells for transfusion prior to angiography (11.2 vs. 17.1, P<0.08). No differences were found that could be attributed to gastric vs. duodenal sources, number of comorbid diseases, organ failure, APACHE score, age, or whether active bleeding was found at angiography. A total of 20 patients (40%) died including 9 of 17 patients operated on in an attempt to salvage angiographic failure. In summary, angiographic embolization should be performed early in the course of bleeding in otherwise critically ill patients.

Alteration of hMSH2 and DNA polymerase beta genes in breast carcinomas and fibroadenomas.

Genomic stability is preserved by error-free DNA replication, post-replicative proofreading, DNA repair, and recombinational events. In essence, DNA repair genes are recognized to play key roles in such stability. We report evidence for expression of the wild-type and a truncated form of DNA polymerase beta (polbeta) proteins, a base-excision repair gene, in breast carcinomas and fibroadenomas, a benign breast disease. An 87-bp deleted variant of polbeta was identified to be prevalent in microsatellite unstable breast tumors and fibroadenomas. A large deletion of 1476 bp, as well as point mutations in human MutS homolog 2 (hMSH2) cDNA, was revealed in breast carcinomas. The protein truncation assay confirmed the 1476-bp deletion as a premature protein. This is the first evidence for variant forms of hMSH2 that are associated with breast cancer. Genomic instability in the hMSH2 and polbeta genes may facilitate the occurrence of mutator phenotype in breast cancer.

Predicting the likelihood of residual disease in women treated for ductal carcinoma in situ.

BACKGROUND: To identify women at risk for residual disease after excision of ductal carcinoma in situ (DCIS), we assessed the relationship between characteristics of the initial biopsy and the presence of residual DCIS at a subsequent operation. STUDY DESIGN: We identified 134 consecutive "paired" operations from 112 women who had undergone 2 or more operations for DCIS between February 1995 and December 1996. Cancer status of the margins, patient age and leading presentation, tumor subtype and grade, and the presence of multifocal-extensive disease were assessed as potential predictors. RESULTS: Residual DCIS was found in 60 patients (45%): in 2 of 12 patients (17%) with negative margins, in 11 of 36 (31%) with close margins (< 2 mm), in 30 of 52 (58%) with positive margins, and in 17 of 34 patients (50%) with margins of unknown status. Patients with positive or unknown margins were 7.7 and 8.3 times, respectively, more likely to have residual disease than patients with negative margins (95% CI 1.1-59.1; 1.1-66.4). Patients with clinical presentations were 8.0 times more likely to have residual disease than patients who presented with abnormal mammograms (95% CI 2.3-27.6). Multifocal-extensive DCIS was associated with residual disease (adjusted odds ratio [OR] = 7.7, 95% CI 2.9-20.5), as was comedo subtype (OR = 2.7, 95% CI 1.1-6.7). CONCLUSIONS: Positive or unknown biopsy margins, a clinical presentation, multifocal-extensive cancer, and the comedo subtype are associated with higher risk of residual DCIS.

Trends in bile duct injuries from laparoscopic cholecystectomy.

Bile duct injuries are a serious complication of cholecystectomy. Laparoscopic cholecystectomies (LC) were originally associated with an increased incidence of injuries. Patients referred to a tertiary center were reviewed to assess the trends in the number, presentation, and management. Seventy-three patients were referred over a 6-year period with a maximum of 17 patients referred in 1992, but the number has not declined substantially over time. The persistent number of referrals is a consequence of ongoing injuries. One third of injuries were diagnosed at LC, and the use of cholangiography has not increased. The number of cystic duct leaks has not decreased and they represent 25% of all cases. The level of injury has remained unchanged with Bismuth types I and II in 37% and types III and IV in 38%. Excluding patients with cystic duct leaks, 58% were referred after a failed ductal repair. Definitive treatment with biliary stenting was successful in 37%, and 34 patients (47%) required a biliary-enteric anastomosis. Complications occurred in 18 patients (25%) including seven with postoperative stricture or cholangitis. No biliary reoperations have been performed at a mean follow-up of 36 months.

Laparoscopic cryoablation of hepatic metastases.

OBJECTIVE: To evaluate the feasibility of laparoscopic cryoablation for the management of hepatic metastases. DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Nine patients were evaluated by laparoscopy for planned laparoscopic cryoablation of hepatic metastases at The Cleveland Clinic Foundation, Cleveland, Ohio, from April 1996 to May 1997. RESULTS: Laparoscopic exploration revealed diffuse extrahepatic disease not identified by preoperative studies in 2 patients. The remaining 7 patients underwent 9 cryotherapy sessions. During 4 of the cryotherapy sessions, ultrasonography demonstrated unrecognized additional treatable hepatic lesions. An average of 3 lesions (range, 2-5) were treated. Operative time averaged 3.5 hours with a mean intraoperative blood loss of 235 mL. One patient had significant intraoperative hemorrhage requiring conversion to open hepatic resection for bleeding control. Eight of the 9 patients tolerated normal diets and ambulated independently on the first postoperative day. Following cryotherapy, 4 of the patients developed fever without an infectious source. One patient developed a postoperative bile leak requiring percutaneous biliary stenting. Postoperative hospital stay averaged 4.5 days (median, 4 days; range, 2-14 days). At a mean follow-up of 9 months, 4 of the 7 patients treated are alive without evidence of disease, 2 are alive with disease, and 1 patient with a pancreatic primary tumor has died of disease. CONCLUSIONS: Laparoscopy with laparoscopic ultrasonography is a useful tool in evaluating patients with hepatic metastases. Laparoscopic cryoablation is feasible and may result in lower postoperative morbidity in patients receiving aggressive treatment for inoperable hepatic metastases.

Successful management of visceral Klippel-Trenaunay-Weber syndrome with the antifibrinolytic agent tranexamic acid (cyclocapron): a case report.

Klippel-Trenaunay-Weber syndrome (KTWS) is a rare, congenital disorder characterized by vascular nevus formation, deep venous thrombosis, varicosities, and hypertrophy of affected tissues. A patient with known thrombosis of his splanchnic circulation and visceral KTWS presented with life-threatening hemorrhage from rectosigmoid varices. Portosystemic shunting was not feasible. Endoscopic sclerosis, variceal ligation, and proctocolectomy were not possible due to the size and number of the varices. Previous treatment with epsilon-aminocaproic acid had been unsuccessful and complicated by thrombophlebitis. Conservative treatment with blood transfusions, cryoprecipitate, fresh frozen plasma, vitamin K, propanolol, and somatostatin analog failed to stop the bleeding. The patient was given the antifibrinolytic agent, tranexamic acid, with cessation of his hemorrhage. Serial thromboelastograms confirmed improved reaction time, coagulation time, clot formation rate, and maximum amplitude. We conclude that tranexamic acid may be a useful adjunct in the medical treatment of high-risk patients with KTWS and other vascular nevi complicated by coagulopathy.

Quantitative classification of breast tumors in digitized mammograms.

The goal of this study was to develop a technique to distinguish benign and malignant breast lesions in secondarily digitized mammograms. A set of 51 mammograms (two views/patient) containing lesions of known pathology were evaluated using six different morphological descriptors: circularity, mu R/sigma R (where mu R = mean radial distance of tumor boundary, sigma R = standard deviation); compactness, P2/A (where P = perimeter length of tumor boundary and A = area of the tumor); normalized moment classifier; fractal dimension; and a tumor boundary roughness (TBR) measurement (the number of angles in the tumor boundary with more than one boundary point divided by the total number of angles in the boundary). The lesion was segmented from the surrounding background using an adaptive region growing technique. Ninety-seven percent of the lesions were segmented using this approach. An ROC analysis was performed for each parameter and the results of this analysis were compared to each other and to those obtained from a subjective review by two board-certified radiologists who specialize in mammography. The results of the analysis indicate that all six parameters are diagnostic for malignancy with areas under their ROC curves ranging from 0.759 to 0.928. We observed a trend towards increased specificity at low false-negative rates (0.01 and 0.001) with the TBR measurement. Additionally, the diagnostic accuracy of a classification model based on this parameter was similar to that of the subjective reviewers.

Clostridium difficile colitis in the critically ill.

UNLABELLED: Morbidity and treatment of Clostridium difficile colitis (CDC) continue to be controversial. Some claim minimum morbidity, which may be a function of differences in patient population and/or bacterial virulence. METHODS: To evaluate the effect of CDC in the critically ill, we retrospectively reviewed the records of 59 intensive care unit patients with CDC who were diagnosed by fecal toxin assays or clinical evidence of pseudomembranous colitis from January 1991 to October 1994. Symptoms, signs, antibiotic regimens, diagnostic tests, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, morbidity, and mortality were analyzed, and results of surgical treatment were compared with the literature. RESULTS: Mean age was 66.4 (17-95) years, with a male to female ratio of 1.8:1. First treatment was metronidazole by mouth in 15 patients (25.4 percent), vancomycin by mouth in 30 patients (50.8 percent), sequential by mouth vancomycin/metronidazole in 3 patients (5.1 percent), and intravenous metronidazole in 5 patients (8.5 percent). Six patients had no medical therapy before surgery or discharge. Ten patients (17 percent) had recurrence and 12 (20.3 percent) required surgery for progressive toxicity or peritonitis. Of three patients who were initially treated by diverting stomas, one died and two required total colectomy (TAC). Two underwent partial resection (1 that was nearly a total colectomy), and seven others had a TAC. Surgical patients had worse mean APACHE II scores at diagnosis (24.4 vs. 19.9; P < 0.001). Thirty-day mortality in surgical patients was 41.7 vs. 14.7 percent in medical patients (P < 0.5). CONCLUSION: Twenty percent of critically ill patients with CDC required operation. TAC and diversion appeared to be more effective surgical treatments than diversion alone.

Pyogenic hepatic abscess: results of current management.

From 1980 to 1991, 56 cases of pyogenic liver abscess were treated at the Cleveland Clinic. The most frequently used treatment was percutaneous catheter drainage of the abscess under computed tomography (CT) guidance (39 patients), followed by CT-guided aspiration without catheter drainage (10 patients). Six patients were initially treated by open operative drainage; another five were operated upon after CT guided drainage had failed. One patient with advanced pancreatic cancer was treated with antibiotics only. The overall mortality rate was 12.5% (7/56). It is clear that the preferred method of treatment for pyogenic hepatic abscess is now CT guided catheter drainage. Operative drainage is reserved for patients who fail to respond to percutaneous drainage or in whom surgery is indicated for other purposes. Aspiration without catheter drainage is a modality that needs further evaluation to define its indications.

Incomplete excision of the gallbladder during laparoscopic cholecystectomy.

Dissection and transection of the cystic duct close to the gallbladder has been advocated as a means of avoiding common bile injury during laparoscopic cholecystectomy (LC). We present three cases in which inadequate identification of the gallbladder-cystic duct junction resulted in incomplete cholecystectomy. In two patients an unsecured gallbladder infundibulum presented as cystic duct leaks and one patient developed recurrent symptomatic cholelithiasis. These cases emphasize the need for complete dissection and visualization of the cystic duct at the gallbladder prior its division and secure ligation during LC.

Partial mastectomy and breast reconstruction. A comparison of their effects on psychosocial adjustment, body image, and sexuality.

BACKGROUND: This retrospective study compared psychosocial adjustment, body image, and sexual function in women who had either breast conservation or reconstruction for early stage disease. METHODS: Questionnaires were completed at a mean of 4 years after surgery by 72 women who had partial mastectomy and 146 women who had immediate breast reconstruction after mastectomy. RESULTS: In general, fewer than 20% of women reported poor adjustment on the domains measured. The two groups did not differ in overall psychosocial adjustment to illness, body image, or satisfaction with relationships or sexual life. There was a specific advantage of partial mastectomy over breast reconstruction in terms of maintaining pleasure and frequency of breast caressing during sexual activity. Women who had undergone chemotherapy had more sexual dysfunction, poorer body image, and more psychological distress. Hormonal therapy and radiation therapy, however, did not measurably affect quality of life. Factors predictive of greater psychosocial distress included a troubled marriage, a poor body image, sexual dissatisfaction, less education, and treatment with chemotherapy. CONCLUSIONS: The choice of local treatment had little psychosexual impact, whereas chemotherapy was associated with long term impairments.

Microsatellite instabilities at five chromosomes in primary breast tumors.

The microsatellite instabilities at nine loci of chromosomes 2p, 8p, 10p and 11p and the nm23-H1 locus on 17q21.3 were studied in primary breast tumors. Alterations in the short interspersed tandem repeats in tumor DNA in the form of either larger allele, smaller allele or LOH were observed. Significantly, a high occurrence of alterations in microsatellite polymorphisms at the ANK1, D8S135 and LPL loci of chromosome 8p (46-54%), the D2S119 locus of chromosome 2p (56%), the D10S197 locus at chromosome 10p (88%), and the nm23-H1 locus of chromosome 17q21.3 (46%) were observed in breast tumors. These results provide the first evidence for genomic instabilities at 2p, 8p and 10p in primary ductal and lobular breast carcinomas. No correlation has been found between the stage of the tumor and microsatellite instability, suggesting that microsatellite instability is an early genetic event in breast carcinogenesis.

Partial mastectomy without radiation is adequate treatment for patients with stages 0 and I carcinoma of the breast.

The treatment of potentially curable carcinoma of the breast has changed from one operation, radical mastectomy, to a flexible approach. At the Cleveland Clinic, we use four types of treatment for primary potentially curable carcinoma of the breast (Stages 0, I and II)--modified radical mastectomy, simple mastectomy, partial mastectomy with postoperative adjuvant radiation therapy and partial mastectomy without radiation therapy. The latter treatment (partial mastectomy without adjuvant radiation) is controversial. We recommend this procedure for patients with T(is) and T1 carcinomas that appear to be localized, without lymph node metastases, Stages 0 and I disease. The overall and disease-free survival rates are similar to those of patients having modified radical or partial mastectomy with radiation. Local recurrence is slightly higher at five years (11.0 percent) as compared with the other procedures, but at ten years, is only 16.1 percent, a figure comparable with patients having partial mastectomy with radiation (14.4 percent). For patients with Stages 0 and I carcinoma of the breast, the addition of postoperative radiation therapy after partial mastectomy seems to be unnecessary.

Breast-conserving surgery: how much is enough?

Breast-conserving operations for the treatment of small, apparently localized invasive breast cancer are now accepted by most surgeons. Still controversial are (1) the size of the primary tumor selected for breast conservation treatment, (2) how much breast tissue must be removed to provide an "adequate" margin to achieve local control, and (3) whether the entire breast needs to be treated by radiation therapy in all patients after adequate partial mastectomy. The results of breast-conserving operations at the Cleveland Clinic are presented and the case for selected, individualized therapy utilizing partial mastectomy without radiation therapy for selected patients with small invasive cancers is made.

Dynamic rehabilitation of the paralyzed face: III: Balanced coupling of oral and ocular musculature from the intact side in the canine.

We have recently demonstrated the feasibility of artificial agonist/antagonist coupling between intact facial and reinnervated strap muscles in the rabbit. The present study broadens this principle to involve bi-level cross-facial innervation. After severing the facial innervation unilaterally in four dogs, a nerve pedicle from a cervical motor nerve was implanted into the orbicularis oris and from the deep temporal nerve into the orbicularis oculi. After neurotization (5.6 months), the pedicles were electrically stimulated to verify muscular response. Graded contraction on the intact side was induced by stimulating the ipsilateral facial nerve with currents of various pulse widths. The resulting compression of a strain gauge on the intact face triggered a two-channel, opto-isolated, pulse width-modulated stimulator to produce agonistic graded contraction at one level of the reinnervated side (e.g., oral) and reciprocal relaxation in its reinnervated counterpart (e.g., ocular). The sophistication of the present model--as compared to the original pilot study--brings us one step closer to dynamic human facial rehabilitation.

Electronic pacing of incapacitated head and neck structures.

Paralysis in the head and neck can affect any motor or mixed cranial nerves and the cervical roots. Most conspicuous deficits, however, involve the larynx and the face. The capacity for denervated striated muscle to undergo reinnervation, and the presence of remaining sources of information, have allowed coordinated rehabilitation of incapacitated cervical neuromuscular systems. The object of further related research should focus on the long-term efficacy of the reinnervated muscle machinery and the potential complexities of electronic integration.