Mariana Berho

Determinants of Recurrence After Sigmoid Resection for Uncomplicated Diverticulitis

AbstractPURPOSE: This study aimed to evaluate the impact of surgery-associated variables on recurrence rates after sigmoid resection for diverticulitis. METHODS: Patients who underwent elective sigmoid resection for uncomplicated diverticulitis between 1992 and 2000 at two tertiary referral centers were followed up for recurrent disease as the primary end point. Recurrence after surgery was defined as left lower quadrant pain, fever, and leukocytosis, with consistent CT and/or contrast enema findings on admission and after six weeks. A logistic regression of the following variables was undertaken: patient demographics, duration of preoperative symptoms, previous admissions and abdominal surgery, surgical access (laparoscopic or open), postoperative complications, splenic flexure mobilization, anastomotic technique (handsewn or stapled), specimen length, inflammation at proximal resection margin, and anastomotic level (colosigmoid or colorectal). The last three variables were defined by the pathologist. Anastomosis level was based on muscle layer configuration (taeniae coli) at the distal resection margin. RESULTS: Two hundred thirty-six patients (105 females) with a mean age of 60.4 (standard deviation, ± 10) years were available for follow-up at 67 ± 30 (range, 11–130) months. The median duration of preoperative symptoms was 18 (range, 12–120) months. All but one (99 percent) patient had at least one admission before surgery. One hundred forty (59 percent) and 96 (41 percent) patients underwent laparoscopic or open resection, respectively. The conversion rate was 13 percent (18 patients) in the former group and the 30-day complication rate was 23 percent, with 0.4 percent 30-day mortality and a 2.1 percent reoperation rate. The splenic flexure was mobilized in 109 patients (47 percent). Anastomoses were fashioned by stapler in 171 patients (73 percent) and were to the rectum in 143 patients (72 percent). Specimen length was 17.9 ± 5.9 (range, 9–47) cm with inflammation at the proximal margin in 30 patients (14 percent). Twelve (5 percent) patients developed a recurrence at a mean of 78 ± 25 (range, 34–109) months with reoperation in one (0.4 percent). The level of anastomosis was the only predictor of recurrence in regression analysis (P = 0.033). Patients with colosigmoid anastomosis had a four times higher risk of having a recurrence compared with patients with colorectal anastomosis (odds ratio, 95 percent confidence interval = 1.12, 14.96). CONCLUSION: Colorectal (rather than colosigmoid) anastomosis was the single predictor of lower recurrence rates after elective sigmoid resection for uncomplicated diverticulitis.

Reliability of histopathologic assessment for the differentiation of recurrent hepatitis C from acute rejection after liver transplantation

Histopathologic assessment is considered essential for the differentiation of recurrent hepatitis C (RHC) from acute cellular rejection (ACR) after liver transplantation (LT); however, there is limited information regarding its reliability. The aim of this study was to determine the interobserver and intraobserver agreement of the histopathologic diagnosis of RHC vs. ACR, and to determine the reliability of specific histopathologic features for the differentiation of RHC from ACR. Liver biopsy specimens from 105 consecutive patients transplanted for hepatitis C virus (HCV)‐related liver disease were studied retrospectively. All the biopsies were performed for evaluation of abnormal liver enzymes within the 1st year after LT. The slides were blindly coded and assessed by 5 liver‐transplant pathologists, practicing at 3 medical centers. The pathologists were asked to render a diagnosis, and determine the severity of the disease. Four of the pathologists were asked to determine the presence and severity of 36 histopathologic features. A total of 34 of the samples were then blindly resubmitted to each of the 4 pathologists to determine the intraobserver agreement. There was a slight agreement (κ = .12) among the 5 pathologists on the histopathologic diagnosis. All 5 pathologists were in agreement on the diagnosis of RHC in only 5 patients (5%) and on the diagnosis of ACR in only 2 patients (2%). The best agreement among any 4 pathologists was fair (κ = .20). Slight to moderate agreement occurred on the main histological features considered to be important in the diagnosis of ACR. Intraobserver agreement ranged from slight (κ = .19) to moderate (κ = .42) among 4 pathologists. In conclusion, the histopathologic differentiation of RHC from ACR after LT had relatively low interobserver and intraobserver agreement rates, and hence showed low reliability. Histopathologic assessment should be used cautiously for the differentiation of RHC from ACR post‐LT. (Liver Transpl 2004;10:1233–1239.)

The oncocytic variant of papillary carcinoma of the thyroid: A clinicopathologic study of 15 cases

The oncocytic variant of papillary carcinoma of the thyroid represents an unusual neoplasm whose clinicopathological features and biological behavior have not been thoroughly characterized. We studied 15 cases of thyroid tumors predominantly composed of oncocytic (oxyphilic) cells that were characterized by showing the classical nuclear features of papillary carcinoma of the thyroid. Thirteen patients were women, and two were men; their ages ranged from 34 to 86 years. The tumors measured from 1 to 4 cm in diameter and were well circumscribed and confined to the thyroid gland in all cases except for one, in whom there was extrathyroidal local extension. Histologically, all tumors showed, at least focally, the formation of papillary structures; in 13 cases the papillary features were found to predominate or were admixed in equal proportion with a follicular pattern of growth, and in two the follicular growth pattern predominated and only abortive, small papillary structures could be found on extensive search. In all cases, the classical optically clear nuclei of papillary carcinoma were present throughout the lesions. Nuclear grooves and intranuclear cytoplasmic inclusions were also a prominent and constant component of these lesions. In 13 cases, the tumors showed the features of Hashimotos or lymphocytic thyroiditis in the surrounding, uninvolved thyroid parenchyma. Follow-up of 1.2 to 13 years (median, 4.5 years) showed the development of cervical lymph node metastases 9 months after surgery in one case; the remainder of patients were alive and free of disease. Oncocytic papillary carcinoma seems to represent a distinctive morphological variant of carcinoma of the thyroid that in our experience does not appear to behave more aggressively than conventional papillary carcinoma. The frequent association of these tumors with autoimmune thyroiditis raises the possibility that the oncocytic changes may be pathogenetically related with the latter process. These tumors should be distinguished from benign and malignant Hurthle cell tumors and other oncocytic thyroid neoplasms that may follow a different biological behavior.

Large cystic lesions of the liver in adults: a 15-year experience in a tertiary center

BACKGROUND Cystic lesions of the liver consist of a heterogeneous group of disorders and may present a diagnostic and therapeutic challenge. Large hepatic cysts tend to be symptomatic and can cause complications more often than smaller ones. STUDY DESIGN We performed a retrospective review of adults diagnosed with large (> or = 4 cm) hepatic cystic lesions at our center, over a period of 15 years. Polycystic disease and abscesses were not included. RESULTS Seventy-eight patients were identified. In 57 the lesions were simple cysts, in 8 echinococcal cysts, in 8 hepatobiliary cystadenomas, and in 1 hepatobiliary cystadenocarcinoma. In four patients, the precise diagnosis could not be ascertained. Mean size was 12.1 cm (range, 4 to 30 cm). Most simple cysts were found in women (F:M, 49:8). Bleeding into a cyst (two patients) and infection (one patient) were rare manifestations. Percutaneous aspiration of 28 simple cysts resulted in recurrence in 100% of the cases within 3 weeks to 9 months (mean 4(1/2) months). Forty-eight patients were treated surgically by wide unroofing or resection (laparoscopically in 18), which resulted in low recurrence rates (11% for laparoscopy and 13% for open unroofing). Four of the eight patients with echinococcal cysts were symptomatic. All were treated by open resection after irrigation of the cavity with hypertonic saline. There was no recurrence during a followup period of 2 to 14 years. Hepatobiliary cystadenomas occurred more commonly in women (F:M, 7:1) and in the left hepatic lobe (left:right, 8:0). Seven were multiloculated. All were treated by open resection, with no recurrence, and none had malignant changes. Cystadenocarcinoma was diagnosed in a 77-year-old man, and was treated by left hepatic lobectomy. CONCLUSIONS Large symptomatic simple cysts invariably recur after percutaneous aspiration. Laparoscopic unroofing can be successfully undertaken, with a low recurrence rate. Open resection after irrigation with hypertonic saline is a safe and effective treatment for echinococcal cysts. Hepatobiliary cystadenomas have predilection for women and for the left hepatic lobe. Malignant transformation is an uncommon but real risk. Open resection is a safe and effective treatment for hepatobiliary cystadenoma, and is associated with a low recurrence rate.

Histologic analysis of the irradiated anal sphincter

AbstractPURPOSE: There is accumulating evidence, both quantitative and qualitative, that pelvic irradiation adversely affects anorectal function. However, histologic evidence of sphincter injury has not been demonstrated. This study was designed to perform histologic assessment of collagen deposition and nerve alteration in the internal anal sphincters of rectal cancer patients who underwent abdominoperineal resection after adjuvant chemoradiation therapy and to correlate the degree of histologic changes with the time interval between chemoradiotherapy and abdominoperineal resection. METHODS: Anal canal specimens were prospectively collected in patients undergoing abdominoperineal resection. Representative slides were cut transversely at the level of the dentate line. Using trichrome and S-100 protein staining, a single pathologist blinded to the patients’ treatment assessed collagen deposition and nerve fiber densities in the internal anal sphincter, respectively. RESULTS: Twelve patients received radiation for rectal cancer (chemoradiotherapy group) and six were treated by surgery alone, including four patients with rectal cancer (1 leiomyosarcoma) and two with Crohn’s disease (control group). There was a trend toward increased fibrosis (replacement of >10 percent of normal structures by collagen) and nerve density in the chemoradiotherapy group compared with the control group (P = 0.08 and P = 0.05, respectively). Nerve density significantly increased as chemoradiotherapy to abdominoperineal resection interval increased (P = 0.04). CONCLUSIONS: Pelvic irradiation results in damage to the myenteric plexus of the internal anal sphincter of patients with rectal cancer; these alterations seem to be time-dependent. A trend toward increased collagen deposition also was observed. Together, these results provide a morphologic basis, which concurs to previously described physiologic and clinical alterations in the anal sphincter of patients irradiated for rectal cancer.

Estrogen Deficiency Accelerates Progression of Glomerulosclerosis in Susceptible Mice

Estrogen deficiency may contribute to the development and progression of glomerulosclerosis in postmenopausal women. The responsiveness to estrogens could be controlled by genetic traits related to those that determine the susceptibility to glomerular scarring. This study was undertaken to determine whether the intensity of the sclerotic response was modified by the estrogen status in sclerosis-prone ROP Os/+ mice. Ovariectomized ROP Os/+ mice developed more severe renal dysfunction and glomerulosclerosis than intact, ie, estrogen sufficient age-matched female mice. Ovariectomized ROP Os/+ exhibited increased accumulation of extracellular matrix, predominantly of laminin, and a marked distortion of the glomerular architecture. We found an increase in macrophage infiltration in the mesangium of ovariectomized ROP Os/+. Estrogen deficiency decreased glomerular estrogen receptor expression in ROP Os/+ mice, which we had previously found to be low in the parental ROP strain. Thus, although physiological estrogen levels in young ROP Os/+ mice could not prevent the development of glomerulosclerosis, estrogen deficiency accelerated the progression of glomerular scarring in this mouse strain. This suggests that estrogen replacement will slow but not prevent the progression of glomerulosclerosis. It underscores the importance of the genetic composition of individuals that determines the susceptibility to diseases as well as the response to treatment.

Resistance to Glomerulosclerosis in B6 Mice Disappears after Menopause

The frequency of chronic renal failure increases with age, especially in women after menopause. Glomerulosclerosis is a common cause of chronic renal failure in aging. We reported that pre-menopausal female C57BL6 (B6) mice are resistant to glomerulosclerosis, irrespective of the type of injury. However, we now show that B6 mice develop progressive glomerulosclerosis after menopause. Glomerular lesions, first recognized in 18-month-old mice, consisted of hypertrophy, vascular pole sclerosis, and mesangial cell proliferation. Diffuse but moderate mesangial sclerosis and more marked hypertrophy were present at 22 months. At 28 to 30 months the glomerulosclerosis was diffuse and increased levels of type I and type IV collagen and transforming growth factor-beta 1 mRNA were present. Urine albumin excretion was significantly increased in 30-month-old mice. Mesangial cells isolated from 28-month-old mice retained their sclerotic phenotype in vitro. Comparison of the effects of uninephrectomy (Nx) in 20-month-old and 2.5-month-old mice revealed a 1.7-fold increase in urine albumin excretion, accelerated glomerulosclerosis, and renal function insufficiency in 20-month-old Nx mice, but not in 2.5-month-old Nx mice. Glycemic levels, glucose, insulin tolerance, and blood pressure were normal at all ages. Thus, B6 mice model the increased frequency of chronic renal failure in postmenopausal women and provide a model for studying the mechanism(s) of glomerulosclerosis in aging women.

Testosterone and 17Β-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice

Podocyte damage and apoptosis are thought to be important if not essential in the development of glomerulosclerosis. Female estrogen receptor knockout mice develop glomerulosclerosis at 9 months of age due to excessive ovarian testosterone production and secretion. Here, we studied the pathogenesis of glomerulosclerosis in this mouse model to determine whether testosterone and/or 17β-estradiol directly affect the function and survival of podocytes. Glomerulosclerosis in these mice was associated with the expression of desmin and the loss of nephrin, markers of podocyte damage and apoptosis. Ovariectomy preserved the function and survival of podocytes by eliminating the source of endogenous testosterone production. In contrast, testosterone supplementation induced podocyte apoptosis in ovariectomized wild-type mice. Importantly, podocytes express functional androgen and estrogen receptors, which, upon stimulation by their respective ligands, have opposing effects. Testosterone induced podocyte apoptosis in vitro by androgen receptor activation, but independent of the TGF-β1 signaling pathway. Pretreatment with 17β-estradiol prevented testosterone-induced podocyte apoptosis, an estrogen receptor-dependent effect mediated by activation of the ERK signaling pathway, and protected podocytes from TGF-β1- or TNF-α-induced apoptosis. Thus, podocytes are target cells for testosterone and 17β-estradiol. These hormones modulate podocyte damage and apoptosis.

The first case report of the use of a zoom videoendoscope for the evaluation of small bowel graft mucosa in a human after intestinal transplantation

BACKGROUND Control of allograft rejection remains the most difficult dilemma in intestinal transplantation. Standard endoscopic surveillance to date has not been always accurate in the diagnosis of rejection. We describe the first application of a zoom video endoscope in monitoring graft mucosa in humans after intestinal transplantation. METHOD A zoom video endoscope, which can magnify the image up to 100-fold, was used in this study. The patient was a 31-year-old man who received an isolated intestinal transplant. Surveillance endoscopy with the zoom video endoscope was performed through the ileostomy. Endoscopic biopsies were done at the same time. RESULTS The zoom video endoscope showed the microscopic architecture of the graft mucosa such as villi and crypts with outstanding quality. We found that an enlargement of the crypt areas appeared to correlate with morphologic changes of early rejection. This finding was reversed with the treatment of rejection. CONCLUSIONS The zoom video endoscope successfully showed the detailed information of intestinal mucosa. The ability to visualize a more representative view of the graft mucosa could lead to better detection of early rejection. A greater experience with this unique method will provide more accurate assessment of the intestinal allograft.

17 Β-estradiol and tamoxifen upregulate estrogen receptor Β expression and control podocyte signaling pathways in a model of type 2 diabetes

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.