Physical co-morbidity among treatment resistant vs. treatment responsive patients with major depressive disorder.

Co-morbid physical illness has been suggested to play an important role among the factors contributing to treatment resistance in patients with major depressive disorder. In the current study we compared the rate of physical co-morbidity, defined by ICD-10, among a large multicenter sample of 702 patients with major depressive disorder. A total of 356 of the participants were defined as treatment resistant depression (TRD) patients-having failed two or more adequate antidepressant trials. No significant difference was found between TRD and non-TRD participants in the prevalence of any ICD-10 category. This finding suggests that although physical conditions such as diabetes, thyroid dysfunction, hypertension, ischemic heart disease, and peptic diseases are often accompanied by co-morbid MDD, they do not necessarily have an impact on the course of MDD or the likelihood to respond to treatment. Marginally higher rates of co-morbid breast cancer, migraine and glaucoma were found among TRD participants. Possible explanations for these findings and their possible relation to TRD are discussed.

The economic impact of depression: resistance or severity?

Treatment-Resistant Depression (TRD) affects 60 to 70% of patients with Major Depressive Disorder (MDD). The economic impact of depression in general, and of TRD specifically, was found to be relatively high. As the course of depression can be defined both by the severity of the disease and by the resistance to treatment, the question of the unique contribution of MDD severity vs. resistance to the economic burden of depression is being raised. One hundred and seven unipolar MDD patients, all treated for at least 4weeks, were enrolled in the study. Patients were assessed for their current MDD severity using the Hamilton Depression Rating Scale (HDRS) and past treatments, and for medical-related costs (number of blood and imaging tests, visits paid to physicians, psychiatric hospitalizations) and incapacity-related costs (number of working days lost) during the last episode. TRD and non-TRD patients were, respectively, 39.3% and 60.7% of the patients recruited for the study. TRD patients had more severe depression, and higher costs for imaging tests, physician visits, psychiatric hospitalizations, and number of working days lost. In addition, higher MDD severity was found to be associated with higher costs. Finally, when controlling for the shared variance of TRD and MDD severity, by using residual scores, TRD was associated with higher costs, but MDD severity was no longer related to costs. While both resistance and severity are associated with higher direct and indirect costs, our findings suggest that TRD may be the main factor in determining the economic burden of depression.

Serious life events among resistant and non-resistant MDD patients.

BACKGROUND: Over 60% of patients with major depressive disorder (MDD) do not respond fully to therapy. Half of them eventually will not respond at all and will be referred to as treatment resistant depression (TRD) patients. Stressful life events were found to be associated with MDD and were also found to affect the course of the disease. We hypothesize that negative life events might be an independent risk factor for TRD. METHODS: One hundred and seven unipolar MDD patients, all treated for at least 4 weeks, were enrolled in the study. Patients were assessed on their psychiatric and medical history, and seven categories of stressful life events. RESULTS: 39.3% of participants were defined as TRD patients and 60.7% as non-TRD. TRD patients had more severe depression, more past suicide attempts, more hospitalizations, longer episodes, and received more benzodiazepines, antipsychotics, and ECT. Job loss and financial stress were more prevalent among the TRD group. Overall, the TRD patients had more negative life events than responders. LIMITATIONS: This is a retrospective study. In addition, the definition of TRD was done dichotomically, therefore the association between number of stressful life events and the degree of resistance was not tested. CONCLUSIONS: Job loss and financial distress were found to predict TRD. The loss of a parent and severe health conditions were not associated with TRD, suggesting that events affecting the development of MDD, do not necessarily affect the treatment outcome.

Physical activity protects male patients with post-traumatic stress disorder from developing severe fibromyalgia.

OBJECTIVES: Fibromyalgia syndrome (FMS) has been associated with various psychiatric and other, ill-defined disorders. We recently showed that fibromyalgia is more prevalent in men suffering from combat-related Post Traumatic Stress Disorder (PTSD). In this paper we analyze the relationship between engagement in physical activity, the psycho-metric traits of PTSD and the future development of FMS. METHODS: Fifty-five male patients, all known to have combat-related PTSD, were investigated for the presence of fibro-myalgia according to the American College of Rheumatology (ACR) criteria. Each patient completed questionnaires characterizing his quality of sleep, and the Sheehan Disability Scale measuring performance in the familial, social and vocational spheres. Additionally, each of the enrollees was interviewed by an experienced psychiatrist, who then completed a Clinician Administered PTSD Scale, a Clinical Global Impression Scale, and calculated an SF-36 score. Each patient was asked whether he exercised often, occasionally or not at all. The data was analyzed by the chi2 test and by ANOVA. RESULTS: PTSD patients who also suffered from FMS had a more severe form of disease as measured by the Clinician Administered PTSD Scale (CAPS) score, 88.2 +/- 14.0 (n = 28) compared to 97.6 +/- 13.2 of patients with PTSD and FMS (n = 27) (p = 0.013, F(d.f 2)-6.61, ANOVA test). Interestingly, engaging in physical exercise was also associated with less severe disease. When the patients were analyzed based on their tender point count (0-5, 6-10, or > 11), the number of tender points decreased with increasing physical activity (p = 0.02, chi2(d.f.-4) = 11.3). CONCLUSION: Physical exercise in male patients with combat-related PTSD provides protection from the future development of fibromyalgia. Furthermore, physical activity is related in this group of patients to a better perception of their quality of life.

Adjuvant radiation trials for high-risk breast cancer patients: adequacy of lymphadenectomy.

BACKGROUND: The recently published, widely publicized adjuvant radiation trials from Denmark and Canada concluded that the addition of postoperative radiotherapy (XRT) to modified radical mastectomy (MRM) and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal patients with breast cancer. Our thesis is that adequate lymphadenectomies were not performed in either study. Consequently, the conclusion to these studies is not applicable to those patients who have undergone adequate surgery. METHODS: To better assess adequate lymph node yield from an MRM, a retrospective review was performed on 215 consecutive patients treated surgically for invasive breast cancer. Data from this review were compared with the surgical data from the above-mentioned radiotherapy trials. RESULTS: In a group of 131 patients who had MRM, the average number of nodes removed was 26 (median, 25), and 75.5% of the specimens had 20 or more lymph nodes. In 73 patients who underwent segmental mastectomy with axillary lymph node dissection, both the average and the median number of lymph nodes removed were 24, and 68.9% had 20 or more nodes. These data compare to the Danish radiation trial in which a median of 7 lymph nodes were removed (with 76% of the patients having 9 or fewer lymph nodes in the specimen) and to the Canadian radiation trial in which a median of 11 lymph nodes were removed. In addition, in our breast cancer patients with positive nodes (84 of 204; 41.2%), 45.2.% (38 of 84) had more than three positive nodes compared with 29.8% in the Danish study and 35% in the Canadian study. CONCLUSIONS: Our surgical data are sufficiently different from those of the Danish and Canadian studies to indicate that, in those studies, incomplete lymph node dissections were performed and that residual disease was left behind in the axilla in some or all of the patients. The addition of XRT in the setting of residual axillary disease may compensate for an inadequate operation and yield an acceptable oncological result; however, these studies did not provide an adequate comparison with a well-performed MRM without XRT. In the absence of documented benefit, XRT should not be routinely added if a complete lymph node dissection has been performed.

Granular cell tumor of the biliary system.

Granular cell tumors (GCT) are rare benign neoplasms of Schwann cell origin which have been found in virtually every location in the body. Their location in the biliary system is unusual, and typically occurs in black females during the fourth decade of life. Forty-eight cases have been reported since 1952. We present two patients treated for obstructive jaundice caused by GCT of the extrahepatic biliary tree. The literature on biliary GCT is reviewed and their management is outlined. Local excision with Roux-y-hepaticojejunostomy was performed in one patient with GCT obstructing the common bile duct at the level of the cystic duct. Pancreaticoduodenectomy was performed on one patient for GCT of the common bile duct involving the ampulla and adjacent pancreas. GCT of the extrahepatic biliary system are rare but should be considered in black females who present with obstructive jaundice in the fourth decade of life. Local excision with cholecystectomy and reconstruction of the biliary remnant is indicated. Primary biliary anastomosis is desired but choledochojejunostomy or hepaticojejunostomy may be necessary. Rarely, pancreaticoduodenectomy may be indicated in GCT of the distal common bile duct.

Tumor aneuploidy in young patients with colorectal cancer.

BACKGROUND: Colorectal cancer in young patients (40 years of age or younger) often is considered to have a worse prognosis than in older patients. The authors studied tumor DNA status and stage of disease to determine whether tumors in younger patients behaved differently from tumors in older patients. METHODS: This retrospective study identified 33 young patients with colorectal cancer treated surgically between 1979 and 1989. The DNA content of the tumors was analyzed by DNA flow cytometry. Results were compared with 75 cases of colon cancer in patients older than 40 years of age. RESULTS: Six of the 33 young patients had inadequate tissue for study. Four patients with ulcerative colitis were excluded. Tumor aneuploidy was present in 14 of 23 young patients (61%; mean age, 35 years) and 46 of 75 older patients (61%; mean age, 71 years). When Dukes staging was performed for the young patients, one had Stage A (4%), nine had Stage B (39%), eight had Stage C (35%), and five had Stage D (22%) disease. The control group had similar staging. The distribution of aneuploid tumors within each Dukes stage was also similar. Twenty-one young patients were available for follow-up. Four (31%) of 13 patients with aneuploid tumors died, whereas none of 8 patients with diploid tumors died. This trend was not statistically significant (P < 0.10). CONCLUSIONS: The frequency of tumor aneuploidy, stage of disease at presentation, and distribution of tumor aneuploidy within each stage was similar when young and old patients with colorectal cancer were compared. There is a trend toward tumor aneuploidy being associated with a poorer prognosis in young patients.

Thallium scintigraphy in the evaluation of mass abnormalities of the breast.

Palpable mass abnormalities of the breast are often difficult to evaluate mammographically, especially in patients with fibrocystic change and dense breasts. The current study evaluates 201TI scintigraphy as a potential test in detecting malignancy and in differentiating malignant from benign masses. Eighty-one female patients underwent thallium scintigraphy of the breast because of palpable breast masses. An additional 30 females with no palpable breast abnormalities were also studied using 201TI. Of 44 patients with palpable breast carcinomas, 42 carcinomas (96%) were detected using 201TI scintigraphy. Three of three patients had other primary breast malignancies that were also detected. In contrast, 19 patients with palpable breast abnormalities shown on biopsy to be benign fibrocystic disease processes were not detectable on thallium studies. Of two patients with fat necrosis, none were detectable. Three of 13 patients had adenomas of the breast (23%) that were detected. The three detectable adenomas were all highly cellular. The smallest detectable carcinoma was an adenocarcinoma measuring 1.3 x 1.1 x 0.9 cm. Thallium-201 scintigraphy of palpable breast lesions is an effective test for evaluation of palpable masses. Sensitivity for detection of malignant masses greater than 1.5 cm is high. Highly cellular adenomas, however, may demonstrate significant 201TI uptake. Benign fibrocystic disease is not detectable with thallium scintigraphy. Thallium scintigraphy of breast lesions is an effective means of differentiating benign from malignant lesions.

Benign schwannoma and parathyroid adenoma occurring in the nonradiated neck: report of two cases.

The late occurrence of multiple neoplasms in the previously radiated neck is a well-known association. However, multiple tumours in the nonradiated neck remain a rare finding. This paper presents two cases of the infrequently seen schwannoma occurring with a parathyroid adenoma without antecedent history of radiation or neurofibromatosis.

Cystic neoplasms of the pancreas.

Cystic neoplasms of the pancreas can be easily misdiagnosed and mistreated by the surgeon unfamiliar with the pathology, natural history, and operative strategy specific to these uncommon tumors. The authors have treated nine patients over a seven-year period involving four cystadenocarcinomas, two mucinous cystadenomas, two serous cystadenomas, and one solid and papillary epithelial tumor. Our experience illustrates the inaccuracies in both clinical and pathologic diagnosis. Suspected cystic neoplasms are optimally managed by resection. Their slow growth and late metastasis permits curative surgery after a previous drainage or bypass procedure. An aggressive surgical approach is therefore warranted, and multimodal treatment with radiation and chemotherapy may be clinically applicable to large, invasive cystadenocarcinomas.

Cystadenocarcinoma of the pancreas: neo-adjuvant therapy and CEA monitoring.

Cystadenocarcinoma of the pancreas is generally considered to be unresponsive to chemotherapy and radiation therapy. We present two cases of laparotomy-proven unresectable cystadenocarcinoma which responded to intravenous 5-fluorouracil (1,000 mg/m2/24 hr x 5 days x 2) and 4,000 rads of radiation therapy. Both patients had objective response with marked shrinkage of the tumor as determined by clinical examination and computed tomography. At reexploration both tumors had become completely resectable with histologically clear margins and negative lymph nodes. Carcinoembryonic antigen (CEA) levels were elevated in both patients at initial presentation (86 and 71 ng/ml). The CEA levels declined to 19.9 and 66.0 ng/ml, respectively, after neo-adjuvant therapy, and both fell to normal levels after resection. Although surgical resection has been considered the only curative therapy for patients with pancreatic cystadenocarcinoma, we suggest that preoperative irradiation and chemotherapy may reduce the size of seemingly unresectable tumors. We also recommend serial CEA determinations in patients with levels initially elevated as a marker of the response to neo-adjuvant and operative therapy.

A complication of the Infusaid pump: duodenal atony reversed by urecholine.

The totally implantable infusion pump (Infusaid pump) for treating metastatic disease to the liver is a new treatment that is gaining widespread acceptance. However, as might be expected for any new major surgical procedure, there are increasing reports of complications. We report a complication in which duodenal atony was caused by the infusion of the chemotherapeutic agent (FUDR) into the stomach and duodenum. The atony was totally reversed by the subcutaneous administration of urecholine.

Malignant melanoma. Practical considerations concerning prophylactic regional lymph node dissection.

Seventy-three patients had 77 prophylactic regional lymph node dissections (PRLND) in addition to wide excision of the primary lesion for clinical Stage I primary malignant melanoma. The preoperative evaluation, surgical procedure, and postoperative follow-up were performed by one surgical oncologist. Seven patients had micrometastatic disease in the regional nodes for a yield of 9.6%. Considering only patients with Clark IV and V melanomas, and Clark III melanomas greater than or equal to 2.00 mm, the yield was 15.6%. The most optimistic, published survival statistics demonstrate a 25% 5-year survival advantage for patients who have PRLND with an incidence of occult nodal disease of 14.3%; thus, even the most optimistic data would predict that only a modest number of patients would actually benefit from surgery. It is difficult to justify PRLND for its therapeutic benefit unless a higher yield of positive-node patients is obtained or the surgical indication is for staging or prognostic information.

Retroperitoneal sarcomas: the role of diagnostic imaging and multimodal management.

Retroperitoneal sarcomas are a varied group of malignancies which have a high rate of recurrence following surgery alone. The majority of the initial recurrences are local in nature, and new therapeutic approaches are clearly needed. Diagnostic imaging and "interventional radiology" have important roles to play in the management of these malignancies, as well as in investigational approaches to therapy. Two cases are presented which illustrate some recent advances in diagnosis and staging of this group of tumors which can be attributed to new cross-sectional imaging techniques, when used in concert with "conventional" imaging methods. The latter include arteriography to guide the placement of intra-arterial catheters for local infusion chemotherapy. CT-guided needle biopsies can be performed to secure a preoperative diagnosis and also to obtain viable tissue for in vitro chemosensitivity assays. A judicious combination of local and systemic chemotherapy, radiation, and surgery may hold promise for better control of this malignancy, similar to the therapeutic advances which have already been obtained with limb sarcomas.

Effect of localized magnetic-induction hyperthermia on the brain. Temperature versus intracranial pressure.

Normal brain and brain tumor temperatures were studied for their effects on intracranial pressure (ICP) in 13 patients who received 37 localized thermochemotherapy treatments for recurrent primary or metastatic brain tumors. Two transient neurologic complications occurred in patients with an elevated initial ICP value; thus, the authors concluded that an initial ICP value of 30 cm H2O or greater may contraindicate brain hyperthermia. It appears that noninvasive brain hyperthermia by magnetic-loop induction can cause an initial rise in ICP value, although a protective mechanism(s) that tends to lower ICP occurs over time, and also at a normal brain temperature of approximately 42.0 degrees C. Possible mechanisms of ICP reduction include direct heating of the hypothalamus with a reduction in pCO2 and the development of tachypnea and hyperpnea with a reduction in pCO2. Hyperthermia applied to the brain should be undertaken only with adequate monitoring of ICP; in addition, extreme caution should be taken in patients with an elevated initial ICP value and in those patients in whom adaptation to elevated pressure does not occur.

Parenteral nutrition, biochemistry and respiratory gas exchange.

Lipid-based total parenteral nutrition (TPN) may have an advantage over glucose-based TPN in certain patients because less carbon dioxide is produced. This conclusion, however, does not properly derive from respiratory quotient (RQ) data. Stoichiometric analysis of glucose and lipid metabolism leads to conclusions similar clinically but at variance conceptually with those based on RQ. Thus, changing from glucose to lipid oxidation is associated with an 11% increase in oxygen consumption, a 23% decrease in carbon dioxide production, and a fall in RQ. In contrast, the diversion of glucose metabolism to synthesis of palmitylstearyloleyl triglyceride results in an 8-fold increase in RQ, but contrary to widely published concepts, the rate of carbon dioxide production falls by 68%. However, even this reduced carbon dioxide production associated with lipogenesis is undesirable because it is not associated with significant ATP production.