Citations

The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) remains poorly understood. Ambiguity exists over the features necessary to establish the diagnosis, treatment efficacy, and prognosis. We identified 99 patients with POEMS syndrome. Minimal criteria were a sensorimotor peripheral neuropathy and evidence of a monoclonal plasmaproliferative disorder. To distinguish POEMS from neuropathy associated with monoclonal gammopathy of undetermined significance, additional criteria were included: a bone lesion, Castleman disease, organomegaly (or lymphadenopathy), endocrinopathy, edema (peripheral edema, ascites, or effusions), and skin changes. The median age at presentation was 51 years; 63% were men. Median survival was 165 months. With the exception of fingernail clubbing (P = .03) and extravascular volume overload (P = .04), no presenting feature, including the number of presenting features, was predictive of survival. Response to therapy (P < .001) was predictive of survival. Pulmonary hypertension, renal failure, thrombotic events, and congestive heart failure were observed and appear to be part of the syndrome. In 18 patients (18%), new disease manifestations developed over time. More than 50% of patients had a response to radiation, and 22% to 50% had responses to prednisone and a combination of melphalan and prednisone, respectively. We conclude that the median survival of patients with POEMS syndrome is 165 months, independent of the number of syndrome features, bone lesions, or plasma cells at diagnosis. Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop.

Abstract Background Papillary thyroid cancer (PTC) has a generally favourable prognosis, but elderly patients with distant metastases or extracapsular invasion fair poorly. In small studies with short follow-up, young patients presenting with such extracapsular invasion and pulmonary metastases have faired well. This retrospective study was undertaken to clarify the long-term prognosis of such patients with advanced PTC. Methods Twenty-one children and young adults (median age 14 (range 6–20) years) presenting with PTC and pulmonary metastases were treated at a single institution between 1947 and 1998. Mean maximal tumour diameter was 4·65 cm. Initial surgical treatment consisted of total thyroidectomy (n = 16), subtotal thyroidectomy (n = 4) and isthmectomy (n = 1), coupled with a variety of lymph node dissections (n = 20). After operation, 19 patients were treated with ablative and incremental doses of iodine-131 until disease free. All patients were placed on suppressive thyroid hormone after operation. Mean length of follow-up was 21 years (range 3 months to 47 years). Follow-up was less than 3 years in four patients. All patients have undergone post-treatment radionucleotide and radiological evaluation. Results Nine of the 21 patients developed recurrent disease. The risk of recurrence at 5 years was 39 (95 per cent confidence interval 14–57) per cent. Eight had cervical lymph node recurrence and no patient developed recurrent pulmonary disease. All patients with identifiable recurrent disease underwent selective lymph node resection, which involved multiple resections in four. At follow-up, 18 patients remain completely free of disease, one patient has recurrent cervical node disease and two patients have died. The disease-free survival at 5 years was 95 (95 per cent confidence interval 86–100) per cent. Cause-specific death occurred in a single patient who died from extensive local disease at age 29 years after 12 years of multiple cervical lymph node recurrences. Conclusion A stepwise treatment approach including total thyroidectomy, high-dose iodine-131 treatment and early surgical reintervention for suspected local recurrent disease allows long-term survival and frequent ‘cure’ for young patients with PTC and concomitant pulmonary metastases.

Abstract Aim The purpose of the study was to determine the risk of postoperative complications and the functional outcome after a hand-sewn ileal pouch–anal anastomosis (IPAA) for ulcerative colitis using a single J-shaped pouch design. Methods Preoperative function, operative morbidity and long-term functional outcome were assessed prospectively in 1310 patients who underwent IPAA between 1981 and 1994 for ulcerative colitis. Results Three patients died after operation. Postoperative pelvic sepsis rates decreased from 7 per cent in 1981–1985 to 3 per cent in 1991–1994 (P=0·02). After mean follow-up of 6·5 (range 2–15) years, the mean number of stools was 5 per day and 1 per night. Frequent daytime and night-time incontinence occurred in 7 and 12 per cent of patients respectively, and did not change over a 10-year period. The cumulative probability of suffering at least one episode of ‘clinical’ pouchitis was 18 and 48 per cent at 1 and 10 years and the cumulative probability of pouch failure at 1 and 10 years was 2 and 9 per cent respectively. Conclusion These results indicate that increased experience decreases the risk of pouch-related complications and that with time the functional results remain stable, but the failure rate increases.

Abstract Background Long-term functional outcome after operative treatment of necrotizing pancreatitis (NP) has not been studied extensively. Methods Pancreatic function, performance status, recurrence of symptoms and other related problems were analysed in 44 consecutive patients successfully discharged from hospital after operative necrosectomy (1983–1995) and followed up completely for a mean of 5 years. Results Clinical pancreatic insufficiency developed in half the patients. Diabetes mellitus (11 patients), steatorrhoea (six) or both (five) were associated with a mean estimate of 52, 66 and 67 per cent parenchymal necrosis respectively. Normal pancreatic function was associated with 27 per cent parenchymal necrosis (P &lt; 0·05). Diabetes worsened while steatorrhoea tended to improve over time. Abdominal pain and pancreatitis recurred in six and two patients respectively. Performance status worsened in four patients because of recurrent pancreatitis and severe steatorrhoea. Poor long-term performance was associated with a higher Acute Physiology And Chronic Health Evaluation II score on admission (mean 14 versus 9). Conclusion NP has prominent effects on long-term pancreatic exocrine and endocrine function in half the patients, but most preserve a good overall functional status. The development of pancreatic insufficiency varies with the extent of pancreatic parenchymal necrosis.

In cultured endothelial cells, the antioxidant, l -ascorbic acid (vitamin C), increases nitric oxide synthase (NOS) enzyme activity via chemical stabilization of tetrahydrobiopterin. Our objective was to determine the effect of vitamin C on NOS function and tetrahydrobiopterin metabolism in vivo. Twenty-six to twenty-eight weeks of diet supplementation with vitamin C (1%/kg chow) significantly increased circulating levels of vitamin C in wild-type (C57BL/6J) and apolipoprotein E (apoE)–deficient mice. Measurements of NOS enzymatic activity in aortas of apoE-deficient mice indicated a significant increase in total NOS activity. However, this increase was mainly due to high activity of inducible NOS, whereas eNOS activity was reduced. Significantly higher tetrahydrobiopterin levels were detected in aortas of apoE-deficient mice. Long-term treatment with vitamin C restored endothelial NOS activity in aortas of apoE-deficient mice, but did not affect activity of inducible NOS. In addition, 7,8-dihydrobiopterin levels, an oxidized form of tetrahydrobiopterin, were decreased and vascular endothelial function of aortas was significantly improved in apoE-deficient mice. Interestingly, vitamin C also increased tetrahydrobiopterin and NOS activity in aortas of C57BL/6J mice. In contrast, long-term treatment with vitamin E (2000 U/kg chow) did not affect vascular NOS activity or metabolism of tetrahydrobiopterin. In vivo, beneficial effect of vitamin C on vascular endothelial function appears to be mediated in part by protection of tetrahydrobiopterin and restoration of eNOS enzymatic activity.

Background— Although 192 Ir intracoronary brachytherapy has been demonstrated to dramatically reduce the recurrence of in-stent restenosis, up to 24% of these patients will still require repeat target-vessel revascularization. The short- and long-term outcomes of repeat percutaneous intervention in this population have not been characterized. Methods and Results— Analysis was performed of all patients enrolled in the GAMMA-I and GAMMA-II brachytherapy trials who underwent repeat percutaneous target lesion revascularization (TLR) because of restenosis. Subjects were divided into 2 cohorts: those who had received 192 Ir brachytherapy and those randomized to placebo. Forty-five (17.6%) of a total of 256 patients whose index treatment was intracoronary radiation therapy and 36 (29.8%) of 121 patients whose index treatment was placebo required repeat percutaneous TLR. The mean time to this first TLR was 295±206 days in the irradiated group and 202±167 days in the placebo group ( P =0.03). Acute procedural success occurred in 100% of irradiated patients and 94% of placebo controls ( P =0.19). After the first TLR, a subsequent TLR was required in 15 (33.3%) of 45 brachytherapy patients versus 17 (47.2%) of 36 placebo failure patients ( P =0.26). There was no significant difference in time to second TLR between the 2 groups. Other long-term major adverse event rates in both groups were comparable to those of other contemporary angioplasty/stenting series. Conclusions— In those patients who “fail” 192 Ir intracoronary brachytherapy for in-stent restenosis, treatment with 192 Ir delays the time to first TLR. Additionally, repeat percutaneous intervention in these patients is safe and efficacious in the short term, with acceptable long-term results.

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause‐specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940–1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient‐years. The 25‐year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940–1949 and 22% during 1950–1959; during 1960–1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950–1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40‐year rates for CSM and TR during 1940–1949 were significantly higher (p = 0.002) than during 1950–1999. During the last 50 years the 10‐year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10‐year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS ? 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near‐total thyroidectomy and conservative nodal excision.

AbstractTo evaluate long‐term survival of patients with gastrointestinal carcinoid tumors and to assess factors that may influence prognosis, 154 patients (49% females, 51% males), median age 62 years (range 12–84 years) treated at our institution during 1972–1982 have been followed long term. Tumor location included the foregut (7%), midgut (62%), and hindgut (30%). Ninety‐five percent of the patients underwent surgical or endoscopic excision of the primary tumor, with overall operative mortality and postoperative morbidity rates of 2.6% and 11%, respectively. At follow‐up, 60 patients (39%) were alive (median follow‐up 18 years; range 1–26 years). The main causes of death included carcinoid tumor burden (32%), unrelated causes (45%), other malignancy (19%), and unknown causes (4%). Observed overall 5‐ and 10‐year survivals were 69% and 53%, respectively. Survival was not related to gender or symptoms at presentation. However, age, embryologic origin, tumor size, depth of invasion, nodal status, and stage of disease proved to be of statistical significance (log‐rank). In a multivariate Cox' model, only older age (> 62 years) [P =0.001, odds ratio (OR) = 3.4) and embryologic origin (midgut versus foregut) (P = 0.045, OR = 0.45) provided independent prognostic power when death from any cause was taken as the end‐point. This study confirms that patient's age and the site of the primary tumor have prognostic significance. Carcinoid tumors are neuroendocrine tumors with a relatively good prognosis, and long‐term survival is possible despite advanced stages of disease.