S-Classification of Sentinel Lymph Node Predicts Axillary Nonsentinel Lymph Node Status in Patients with Breast Cancer

Background One-half of breast cancer patients with positive sentinel lymph node (SN) have no further metastases in the axillary lymph node basin. The aim of the present study was to identify patients with positive SN who are unlikely to have further metastases in the axillary lymph node basin, using a new classification of SN, namely the S-classification. Methods Specimens of positive SN were subjected to a pathological review according to the previously published S-classification. S-stages of positive SN were correlated with the status of further metastases in the axillary lymph node basin after axillary lymph node dissection (ALND). Results Of 117 patients who underwent sentinel lymph node biopsy, 36 (30.8%) had a positive SN and were subjected to level I and II ALND. The occurrence of positive nonsentinel nodes was significantly related to the S-stage of SN. No patient with stage SI had additional metastases in the nonsentinel lymph nodes, while 14.3% of patients with SII stage disease and 60.9 % of patients with SIII disease had other non-SN that were metastatic. Conclusion S-stages of positive SN are highly predictive for axillary nonsentinel node status. Especially patients with SI sentinel node metastases appear to be at low risk for further nonsentinel node metastases.     

Gamma Knife surgery for adrenocorticotropic hormone-producing pituitary adenomas after bilateral adrenalectomy

OBJECT: Patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas may require a bilateral adrenalectomy to treat their Cushing's disease. Approximately one third of these patients, however, will experience progressive enlargement of the residual pituitary adenoma, develop hyperpigmentation, and have an elevated level of serum ACTH. These patients with Nelson's syndrome can be treated with Gamma Knife surgery (GKS). METHODS: The prospectively collected University of Virginia Gamma Knife database of patients with pituitary adenomas was reviewed to identify all individuals with Nelson's syndrome who were treated with GKS. Twenty-three patients with a minimum of 6 months of follow up were identified in the database. These patients were assessed for tumor control (that is, lack of tumor growth over time) with neuroimaging studies (median follow-up duration 22 months) and for biochemical normalization of their ACTH levels (median follow-up duration 50 months). Neuroimaging follow-up studies were available for 22 patients, and endocrine follow up was available for 15 patients in whom elevation of ACTH levels was documented prior to GKS. In the 22 patients in whom neuroimaging follow-up studies were available, 12 had a decrease in tumor size, eight had no tumor growth, and two had an increase in tumor volume. Ten of 15 patients with elevated ACTH levels prior to GKS showed a decrease in their ACTH levels at last follow up; three of these 10 patients achieved normal ACTH levels (< 50 pg/ml) and the other five patients with initially elevated values had an increase in ACTH levels. Ten patients were thoroughly evaluated for post-GKS pituitary function; four were found to have new pituitary hormone deficiency and six did not have hypopituitarism after GKS. One patient suffered a permanent third cranial nerve palsy and four patients are now deceased. CONCLUSIONS: Gamma Knife surgery may control the residual pituitary adenoma and decrease ACTH levels in patients with Nelson's syndrome. Delayed hypopituitarism or cranial nerve palsies can occur after GKS. Patients with Nelson's syndrome require continued multidisciplinary follow-up care. Given the difficulties associated with management of Nelson's syndrome, even the modest results of GKS may be helpful for a number of patients.     

Perforated Diverticulitis with Generalized Peritonitis: Low Stoma Rate Using a “Damage Control Strategy”

Purpose

Optimal surgical management of perforated diverticulitis of the sigmoid colon has yet to be clearly defined. The purpose of this study was to evaluate efficacy of a “Damage Control Strategy” (DCS).

Materials and methods

Patients with perforated diverticulitis of the sigmoid colon complicated by generalized peritonitis (Hinchey III and IV) surgically treated according to a damage control strategy between May 2011 and February 2017 were enrolled in the present multicenter retrospective cohort study. Data were collected at three surgical centers. DCS comprises a two-stage concept: [1] limited resection of the perforated colon segment with oral and aboral blind closure during the emergency procedure and [2] definitive reconstruction at scheduled second laparotomy (anastomosis???loop ileostomy or a Hartmann’s procedure) after 24–48?h.

Results

Fifty-eight patients were included into the analysis [W:M 28:30, median age 70.1 years (30–92)]. Eleven patients (19%) initially presented with fecal peritonitis (Hinchey IV) and 47 patients with purulent peritonitis (Hinchey III). An anastomosis could be created during the second procedure in 48 patients (83%), 14 of those received an additional loop ileostomy. In the remaining ten patients (n?=?17%), an end colostomy was created at second laparotomy. A fecal diversion was performed in five patients to treat anastomotic complications. Thus, altogether, 29 patients (50%) had stoma at the end of the hospital stay. The postoperative mortality was 9% (n?=?5), and median postoperative hospital stay was 18.5 days (3–66). At the end of the follow-up, 44 of 53 surviving patients were stoma free (83%).

Conclusion

The use of the Damage Control strategy leads to a comparatively low stoma rate in patients suffering from perforated diverticulitis with generalized peritonitis.

     

Prognostic significance of tumour size in patients after tumour nephrectomy for localised renal cell carcinoma

OBJECTIVES: Staging of the primary tumour is accepted as the most important prognostic factor in organ confined renal cell carcinoma. METHODS: The outcome of 286 patients with non-metastatic RCC treated by radical nephrectomy at our institution between 1968 and 1992 was evaluated retrospectively. The median follow-up was 114 +/- 62.6 months. In T1/T2 tumours, the validity of tumour size cut-off points for predicting survival outcome was tested. RESULTS: According to the 1997 TNM classification, 168 patients (59%) showed pathological stage T1 (72 stage T1a, 96 stage T1b), 30 (10%) showed stage T2, 84 patients (29%) demonstrated T3 tumours (53 stage T3a, 31 stage T3b), and 4 patients (2%) presented with T4 tumours. The median survival estimated by Kaplan-Meier analysis for T1a, T1b, T2, T3a, T3b and T4 tumours was over 300 months, 187.0 +/- 32.76; 177.0 +/- 1.21; 121.0 +/- 2.57; 124.0 +/- 11.82 and 52.0 +/- 18.38 months, respectively. Regarding survival in T1/T2 tumours Cox regression analysis yielded the highest significance level for a tumour size cut-off point at 4 cm (p = 0.003; 95%CI 1.511-6.991), but no prognostic value for a cut-off point at 7 cm (T1 vs. T2) (p = 0.375; 95%CI 0.655-3.071). CONCLUSIONS: Tumour size is an important prognostic factor in patients with organ confined RCC. The recently specified new cut-off point of 4 cm for T1a/T1b tumours is feasible for separating groups with different survival after tumour nephrectomy and should be considered as the new boundary between T1 and T2 stages. Hence, a more accurate prediction of prognostic differences between these groups should be possible.     

Successful treatment of irreversible hemorrhagic shock in dogs with fructose-1,6 diphosphate and dichloroacetate

Hemodynamic and metabolic effects of fructose-1,6-diphosphate (F.D.P.) and dichloroacetate sodium (D.C.A.) administration were studied in 17 mongrel dogs during experimentally induced hemorrhagic shock using a modified Wigger's technique. During the oligemic period, which was maintained for 3 hours, a control group of animals (A) received a 5% glucose solution at a rate of 3 mg/kg/min, while the treated group (B) received D.C.A. (175 mg/kg for 30 minutes) and F.D.P. (5 mg/kg/min) as aqueous solutions. After retransfusion of the shed blood, both groups of animals were left to recover. All eight dogs of the control group died within 3 hours following the experiment, while six out of the nine treated dogs survived during a week of follow-up (p = 0.007). Two hours after retransfusion, blood pressure and cardiac index in group B returned to control levels (115 +/- 4.8 mmHg and 0.097 +/- 0.008 liters/min/kg), while group A demonstrated a rapid and progressive deterioration (64 +/- 9.7 mmHg and 0.041 +/- 0.005 liters/min/kg). Severe core hypothermia (down to 33.3 degrees C) developed in group A dogs despite retransfusion, while a normal core temperature was maintained in the treated dogs. Calculated oxygen consumption during the oligemic period was significantly higher in group B animals despite similar calculated oxygen delivery in both groups of animals. Hyperlactemia was significantly lower in group B animals despite F.D.P. administration. This can be attributed to the addition of D.C.A. to the treatment. F.D.P. and D.C.A. administration prevented the occurrence of respiratory failure resulting, most probably, from respiratory muscle fatigue owing to depressed metabolic rate and increased lactate formation in these muscles during the shock period. It is suggested that administration of F.D.P. and D.C.A. during hemorrhagic shock in dogs has a favorable effect on the outcome of this life-threatening condition.     

Identification of cDNA clones encoding a precursor of rat liver cathepsin B.

Recent studies have suggested that many lysosomal enzymes, including cathepsin B (EC 3.4.22.1), may be synthesized as larger precursors and proteolytically processed to their mature forms. To determine the structure of the primary translation product of cathepsin B, we have screened a phage cDNA library for clones encoding rat liver cathepsin B. We synthesized two extended DNA oligonucleotides to use as hybridization probes: a 50-mer corresponding to the coding segment for residues 215-231 of mature cathepsin B and a 54-mer corresponding to residues 117-134. After screening 600,000 plaques, five clones were obtained that hybridized to the 32P-labeled 50-mer; of these, two (lambda rCB3 and lambda rCB5) also reacted with the 54-mer. DNA sequence analysis confirmed that lambda rCB3 and lambda rCB5 both encoded rat liver cathepsin B, and the translated sequence is in agreement with the sequence determined [Takio, K., Towatari, T., Katunuma, N., Teller, D. C. & Titani, K. (1983) Proc. Natl. Acad. Sci. USA 80, 3666-3670], except for a tryptophan for glycine substitution at residue 78 and the presence of two amino acids at the junction site of the light and heavy chains. Moreover, the DNA sequence reveals an open reading frame extending beyond the 5' (NH2 terminus), and the predicted COOH terminus of the coding sequence for the mature protein is extended by six amino acids. These results confirm that the biosynthesis of cathepsin B involves a larger precursor form and demonstrate the effectiveness of long oligonucleotide probes for screening to detect rare cloned mRNAs.     

Seasonal Changes in the Incidence of Transient Global Amnesia

MethodsEvery patient with acute presentation of amnesia at our medical center is hospitalized for observation and evaluation. We reviewed the monthly occurrence of TGA in our patient population between 2000 and 2014, and compared this to non-TGA hospitalizations during the same time period.ResultsDuring the analysis period, 154 patients who met the criteria for TGA were hospitalized, as well as 259,007 non-TGA hospitalizations. The annual occurrence of TGA ranged from 5 to 16 hospitalizations. There were 91 TGA events in women and 63 in men, in subjects aged 62.8±10.6 years (mean±SD). The incidence was maximal during December [odds ratio (OR)=2.83, 95% confidence interval (CI)=1.20–6.67] and March (OR=2.77, 95% CI=1.17–6.56), and minimal from April to August. The incidence exhibited an increase followed by a decrease from October to February. A seasonal trend was observed as well, with incidence peaks occurring in winter (OR=1.82, 95% CI=1.12–2.96) and spring (OR=1.80, 95% CI=1.10–2.94).ConclusionsOur findings suggest that the incidence of TGA exhibits seasonal variations. This observation may help to improve the understanding of the pathophysiology underlying TGA.     

Autonomization of free flaps in the oral cavity: A prospective clinical study

Controversy exists over how long a free flap is dependent on its pedicle and if neovascularization is different between flap types, recipient sites, and irradiated and nonirradiated patients. An understanding of the timing of this process should optimize the safety of secondary procedures involving the flap. In a prospective clinical study, hemoglobin oxygenation and capillary flow were measured in 50 flaps (25 forearm flaps, 15 osteocutaneous fibula flaps, and 10 anterolateral thigh flaps) 4 and 12 weeks postoperatively. The flaps were located at the floor of the mouth, cheek, or tongue (n = 39) or at the hard or soft palate (n = 11). Measurements were carried out using the O2C monitoring system under temporary digital occlusion of the pedicle. After 4 weeks, 17 free flaps were found to be autonomized indicated by the O2C measurements comparing both values before and after digital compression of the vascular pedicle. After 12 weeks, 41 patients had completion of free flap autonomization, as indicated by the HbO(2) and CF before and after pedicle compression. The location of free flap in the lower jaw (P < 0.0001 after 4 weeks, P = 0.013 after 12 weeks), fasciocutaneous radial forearm flaps after 4 weeks (P < 0.0001), and not irradiated recipient site after 4 weeks (P = 0.014) were found to be positive factors significantly influencing autonomization. In conclusion, free flap autonomization depends on several variables which should be considered before further surgery after free flap reconstruction as the transferred tissue can be still dependent on its pedicle.     

Repair of thoracic aortic aneurysm due to noninfectious aortitis

Abstract Background and aim: Isolated thoracic aortitis (ITA) is a newly‐defined pathological entity with a still‐unknown etiopathology and with some potential relationship to IgG4‐related systemic disease. We investigated patients on whom the ascending aorta was operated to identify the clinical and histopathological features of ITA and its relationship to IgG4‐related systemic disease. Methods: Two hundred fifty‐one patients underwent replacement of the ascending aorta. Retrospective review of all histological reports was done to identify noninfectious aortitis. Immunohistochemical analysis of resected specimens was performed in all cases. Results: We found 11 (4.4%) patients with noninfectious aortitis aged 52 to 79 years; nine of the patients were female. All patients underwent ascending aorta replacement. The 30‐day mortality was 0. During the follow‐up period (median 12 months) four patients died (two of them because of progression of aortic disease). None of the seven living patients developed any IgG4‐related diseases, and all had normal serum levels of IgG and IgG4. Conclusions: Surgical treatment of ITA has acceptable short‐ and mid‐term results. Because follow‐up serum levels of IgG and IgG4 were normal in survivors, postoperative corticosteroid therapy may not be indicated in patients in the absence of active vasculitis.     

Prednisone metabolism in recipients of kidney or liver transplants and in lung recipients receiving ketoconazole

BACKGROUND: Actual prednisone exposure in low-dose prednisone regimens, in part determined by cytochrome P450 metabolism, has been shown to be important for allograft survival. METHODS: Prednisolone (the principal active metabolite of prednisone) metabolism was determined in eight nontransplant patients and in transplant recipients receiving oral prednisone maintenance therapy (20 kidney and 6 liver recipients receiving cyclosporine [CsA] and eight lung recipients receiving ketoconazole and CsA or tacrolimus [FK506]). RESULTS: Prednisolone area under the curve (AUC)-dose-normalized (PNAUCn) to 1 mg/kg was 8,288+/-1,513 ng.hr/mL in kidney recipients, versus 4,826+/-999 ng/mL per hr in healthy subjects (P<0.001); it was also increased in liver recipients versus healthy subjects (11,456+/-1,214 ng.hr/mL, P<0.001). Liver recipients also metabolized prednisolone more slowly than kidney recipients (P<0.001). PNAUCn in lung recipients was similar in kidney recipients despite the effect of ketoconazole to slow CsA metabolism. In kidney transplant recipients, the rate of CsA metabolism was correlated with the rate of prednisolone metabolism (r=0.54, P=.026). Basal cortisol levels in all transplant recipients were lower than in healthy subjects, suggesting more prednisolone exposure in transplant patients. CONCLUSIONS: Prednisolone metabolism is slower in solid-organ transplant recipients than in healthy subjects. The slower metabolism of prednisolone, particularly in liver recipients, may help explain the immunologic effectiveness of low-dose prednisone regimens in these patients.