Infiltrating lobular carcinoma of the breast presenting as gastrointestinal obstruction: a mini review.

One in twelve American women will develop breast cancer, with infiltrating lobular carcinoma (ILC) comprising approximately 15% of these cases. The incidence of ILC has been increasing over the last several decades. It has been hypothesized that this increase is associated with combined replacement hormonal therapy. Although pathologically distinct from infiltrating ductal carcinoma (IDC), ILC is treated in the same manner as IDC. However, ILC demonstrates significantly different patterns of late local recurrence and distant metastasis. The incidence of extra-hepatic gastrointestinal metastases is reported to be 6% to 18%, with stomach being most common. Herein, we present a brief review of the literature and a typical case involving ILC initially presenting as a small bowel obstruction. Evidence suggests that the late clinical patterns of ILC are distinctly separate from IDC and physicians need be cognizant of its late local recurrence and unique late metastatic pattern. Different follow up strategy should be entertained in patients with ILC.

Severe hemoperitoneum after patient self-induced fecal evacuation.

An increasing incidence of rectal injuries following patient self-induced harmful acts, aimed to sexual or laxatives porpouses, is a fact reported in literature (El-Ashaal et al., 2008). We herein report a case of severe hemoperitoneum related to a middle and upper rectal third seromuscolar tear caused by a self-induced fecal evacuation by means of an arrow with a covered cork tip. An urgent intestinal diversion by means of a Hartmann's operation was performed. The clinical case is presented in relation to the literature debate, regarding the issue of primary repair or resection and anastomosis versus fecal diversion for penetrating rectal injuries (Fabian, 2002; Cleary et al., 2006; Office of the Surgeon General, 1943; Busic et al., 2002). In conclusion, the importance of avoiding an anastomotic breakdown in a patient undergoing a hemorrhagic shock is highlighted.

Inflammation in venous disease.

Chronic venous disease (CVD), mainly due to venous reflux or, sometimes, to venous outflow obstruction, produces a microcirculatory overload leading to the impairment of venous drainage. Venous drainage depends primarily on a major hemodynamic parameter called trans-mural pressure (TMP). TMP is increased in patients affected by CVD, leading to impaired tissue drainage, and, consequently, facilitating the beginning of the inflammatory cascade. Increased TMP determines red blood cell extravasation and either dermal hemosiderin deposits or iron laden-phagocytes. Iron deposits are readily visible in the legs of all patients affected by severe CVD. Local iron overload could generate free radicals or activate a proteolytic hyperactivity of metalloproteinases (MMPs) and/or downregulate tissue inhibitors of MMPs. These negative effects are particularly evident in carriers of the common HFE gene's mutations C282Y and H63D, because intracellular iron deposits of mutated macrophages have less stability than those of the wild type, inducing a significant oxidative stress. It has been demonstrated that such genetic variants increase the risk of ulcers and advance the age of ulcer onset, respectively. The iron-dependent vision of inflammation in CVD paves the way to new therapeutic strategies including the deliberate induction of iron deficiency as a treatment modality for non-healing and/or recurrent venous leg ulcers. The inflammatory cascade in CVD shares several aspects with that activated in the course of multiple sclerosis, an inflammatory and neurodegenerative disease of unknown origin in which the impairment of cerebral venous outflow mechanisms has been recently demonstrated.

Radiolabelled somatostatin analogs for diagnosis and radio-guided surgery of neuroendocrine breast cancer undetectable with conventional imaging procedures.

Some neoplasms are classified as primary neuroendocrine tumours (NETs) because of their positivity for neuroendocrine markers [chromogranins A and B (CgA, CgB) and neuron-specific enolase (NSE)]. Neuroendocrine differentiation has been reported, for example, in both "in situ" and infiltrating breast cancer. Diagnosis of NET is bio-humoral (CgA, NSE, synaptophysin) and instrumental. Even if the final diagnosis is made by open biopsy, radionuclide imaging using radiolabelled somatostatin analogs, such as In-111 pentetreotide, may detect neuroendocrine primary tumours and metastases before they become detectable using traditional and advanced imaging modalities [mammography (MX), ultrasound (US) and magnetic resonance imaging (MRI)]. When neuroendocrine breast lesions are not detectable, radio-guided surgery (RGS) is able to localise cancer. We report a case of a woman with a palpable lymph node in the left axilla. She underwent a US-guided lymph node biopsy, which was positive for massive metastases, probably of neuroendocrine breast origin. Mammary plus axillary US showed only lymphadenopathy in the left axilla. MX and breast MRI were negative. Neoplastic markers (CEA, CA 15.3, CA 125 and CA 19.9) were negative too. On the other hand, neuroendocrine markers (NSE and CgA) were positive. A whole body scintigraphic scan plus thorax and abdomen single photon emission computed tomography (SPECT) with In-111 pentetreotide (222 MBq; 6 mCi) showed an uptake in the left mammary gland. No other pathological localisations were observed. The day after the intravenous injection of In-111 pentetreotide, the patient underwent RGS breast tumour resection and left axillary lymphadenectomy. In conclusion, we would like to emphasise: (1) the role of radionuclide imaging for the detection of breast NETs in relation to conventional diagnostic procedures; (2) the role of RGS in localising and removing a non-palpable breast NET that was undetectable with the use of conventional imaging techniques.

Use of preoperative lymphoscintigraphy and intraoperative gamma-probe detection for identification of the sentinel lymph node in patients with papillary thyroid carcinoma.

AIMS: Lymph node metastases for papillary thyroid carcinoma are associated with an increased incidence of locoregional recurrence. The use of preoperative lymphoscintigraphy and intraoperative gamma probe detection to localize the sentinel lymph node in papillary thyroid carcinoma was investigated. METHODS: From February 2004 to December 2005 the sentinel lymph node technique was studied in 64 consecutive patients with cytological evidence of papillary thyroid carcinoma. The day before surgery, patients were submitted to US-guided peri-tumoural injection of the radiotracer and a lymphoscintigraphy was performed. In the operating room a total thyroidectomy was done, and thanks to a hand-held gamma probe the sentinel lymph node and all lymph nodes, belonging to the sentinel node compartment, were removed. RESULTS: The gamma probe identified the sentinel lymph node in 62 patients (96.8%). We found 48 (77.5%) sentinel lymph node without metastases; 12 (19.3%) with metastases and 2 (3.2%) with micrometastases. In 7 cases (11.3%), with a negative sentinel lymph node, metastases in other nodes of the same region were recorded. In 22 cases (34.3%) the ultrasound give an erroneous indication (P=0.004). Five patients (8.0%), 4 with multifocal cancer, had a positive postoperative lymphoscintigraphy. CONCLUSION: This study shows that the sentinel lymph node technique for papillary thyroid carcinoma is feasible, repeatable, and more accurate than preoperative ultrasound. In cases of multifocal thyroid lesions more patients should be enrolled to establish the utility of the radio-guided technique.

Primary breast cancer features can predict additional lymph node involvement in patients with sentinel node micrometastases.

OBJECTIVE: The aim of this retrospective study was to identify biological features of primary breast cancer from which to predict the presence of further axillary involvement in patients bearing micrometastases in the sentinel lymph node (SLN). METHODS: From a starting group of 690 patients, we isolated patients with micrometastases in the SLN. Those patients were classified according to the presence/absence of further metastases in nonsentinel lymph nodes (NSLNs). We examined primary tumor features to identify any relevant difference. Analysis of primary tumors evaluated histology, tumor size, lymphovascular invasion, mitotic index (Mib-1), estrogen and progesterone receptor status (ER/PR status), C-erb B-2 (HER-2/neu) expression and amplification, and p53 expression. Chi square analysis for statistical significance was applied. RESULTS: Of the original 690 patients, 296 showed some kind of metastases in the SLN; 238 patients had gross metastases in the SLN. After axillary lymph node dissection (ALND), 102 patients (43%) had NSLNs with metastases, and 136 (57%) had negative axillary non-sentinel nodes. Another 58 patients harbored solitary micrometastases in the SLN. After ALND, 8 (14%) patients had further NSLN involvement, and 50 (86%) had negative axillary nodes. CONCLUSIONS: Analysis of the primary breast lesion in patients with micrometastatic SLN and metastatic NSLNs revealed the presence of lymphovascular invasion, Mib-1 index > 10%, and tumor size > 2 cm. Patients without lymphovascular invasion, Mib-1 < 10% and T size < 2 cm could avoid further ALND.

[Emergency surgery for complicated colorectal cancer. Retrospective study]. / Trattamento chirurgico del cancro colorettale complicato. Studio retrospettivo.

INTRODUCTION: Emergency surgery for the complications of colorectal cancer poses a significant surgical problem with published mortality rates as hight as 25% to 30%. We reviewed the results of the analysis and quantification of the influence of complications on the outcome of the patients who underwent emergency colectomy for colorectal cancer. MATERIALS AND METHODS: Retrospective study of the clinical features from, a series of 63 patients operated on from 1991 to 1997 (12% of all colorectal cancer operations in the same period). The correlations between complications and cancer stages were estimated by the KW (ANOVA method). RESULTS: Fifty-three patients underwent colorectal resection for intestinal occlusion (84%), 5 for perforation (8%) and 5 for lower gastrointestinal bleeding (8%). When the cancer complications were correlated to the different cancer stage at operation, the complications rate were 32%, 32%, and 36% in the stage II, stage III, and stage IV, respectively. This data was statistically significant: (KW = 58, p = 0.0001). The overall mortality rate was 8% (5 patients) and the total postoperative morbity rate was 32% (21 patients). The overall 5-year, 3-year, and 1-year survival was 47%, 48%, and 76% respectively. CONCLUSIONS: Emergency surgery for complicated colorectal cancer can be performed safely with low postoperative morbidity and mortality rate and can be advocated to realize both short and long-term survival rates comparable to elective surgery; the KW test supports the hypothesis that the a complication in the natural history of colorectal cancer doesn't correlate with the stage of disease.

Regional variations of insulin-like growth factor I (IGF-I), IGF-II, and receptor type I in benign prostatic hyperplasia tissue and their correlation with intraprostatic androgens.

Benign prostatic hyperplasia (BPH) is an androgen-dependent disease; it originates exclusively in the inner prostate, which includes tissue surrounding the urethra. Stromal-epithelial interaction has a pivotal role in the regulation of the development and growth of the prostate, and locally produced peptide growth factors are considered important mediators of this interaction. Insulin-like growth factor I (IGF-I) and IGF-II, acting mainly through type 1 IGF receptor (IGFR1), have mitogenic and antiapoptotic effects on epithelial and stromal prostatic cells. In this study the expression of IGF-I, IGF-II, and IGFR1 messenger ribonucleic acid (mRNA), the immunoreactive content of IGF-I (irIGF-I) and IGF-II (irIGF-II) were determined in periurethral, intermediate, and subcapsular regions of BPH tissue to verify their possible regional variation; a correlation to the tissue levels of dihydrotestosterone (DHT) and 3 alpha-androstanediol (3 alpha Diol) was also determined to verify their possible androgen dependence. Prostates were removed by suprapubic prostatectomy from 14 BPH patients and sectioned in the periurethral, intermediate, and subcapsular regions. Gene expression of IGF-I, IGF-II, and IGFR1 was evaluated by semiquantitative RT-PCR, using beta-actin as a control. irIGF-I was measured by RIA, and irIGF-II was measured by IRMA after acidification and chromatography on Sep-Pak C(18) cartridges. DHT and 3 alpha Diol concentrations were evaluated by RIA after extraction and purification on Celite microcolumns. IGF-II and IGFR1, but not IGF-I, mRNA was higher in the periurethral than in the intermediate (P < 0.05) and subcapsular (P < 0.01) region. Also, prostatic levels of irIGF-II, expressed as picomoles per g tissue, were higher in the periurethral (20.84 +/- 1.84) than in the intermediate (14.81 +/- 2.11; P < 0.05) and subcapsular (10.88 +/- 1.21; P < 0.001) region. No significant differences were found in irIGF-I content. Considering prostatic androgen levels, DHT and 3alphaDiol presented a regional variation, with the highest concentrations in the periurethral region. IGF-II mRNA and irIGF-II levels were positively correlated with both DHT and 3 alpha Diol content. These results demonstrate that in BPH tissue a greater IGF-II activity is present in the periurethral region, the site of origin of BPH. Moreover, we can hypothesize that the tissue androgen content may modulate prostatic production of IGF-II, acting at the transcriptional and probably the posttranscriptional level. Therefore, even though further studies will need to confirm this hypothesis, DHT may increase IGF-II activity, mainly in the periurethral region, which, in turn, induces, through IGFR1, benign proliferation of both epithelial and stromal cells, characteristic of BPH.

[Malignancy: treatment and prognosis of gastrointestinal and pancreatic endocrine neoplasia: retrospective study of a series of 16 cases]. / Malignità: trattamento e prognosi delle Neoplasie Endocrine Gastrointestinali e del Pancreas: studio retrospettivo su una serie di 16 casi.

The aim of this study was to review our experience with endocrine tumours of the gastrointestinal tract and pancreas (ETGIP). Between February 1991 and March 2000, sixteen patients with ETGIP were operated on at our institution. Of these patients we reviewed preoperative symptoms, diagnostic techniques (ultrasound, CT, MRI, radiolabelled octreotide scintigraphy, angiography, immunohistochemical study), treatment (surgical operation, neoadjuvant and adjuvant chemotherapy, and radiometabolic therapy) and survival. Nine patients (56%) had a carcinoid tumour, three (19%) an unspecified endocrine tumour, and four (25%) an endocrine tumour associated with a non-endocrine neoplasm. Only five patients (31%) had a preoperative diagnosis of endocrine tumour. Eight patients (50%) had metastatic disease at the time of the operation. All patients without preoperative metastasis (eight patients, 50%) are still alive without recurrent disease, with a mean postoperative survival of 36 months (12-60 months). Of eight patients with metastatic disease, six (75%) died after a mean of 20.5 months (3-60 months) and two (25%) are still alive with the disease after 3 and 6 months, respectively. These data show that presence of metastasis strongly influence survival. Furthermore, survival of patients with metastatic disease seems to be longer as compared to other gastrointestinal tract malignancies. ETGIP are more common and aggressive than previously believed and, therefore, early diagnosis is crucial for cure. Nowadays, however, new diagnostic tools such as radiolabelled octreotide scintigraphy are available for diagnosis and postoperative follow-up. The optimal treatment for ETGIP is a multimodal approach with surgical operation, chemoradiation, radiometabolic, and genetic therapies.

Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia.

BACKGROUND: The n-hexane lipido-sterol extract of Serenoa repens (LSESr, Permixon, Pierre Fabre Medicament, Castres, France), a phytotherapeutic agent used in the treatment of benign prostatic hyperplasia (BPH), has a multisite mechanism of action including inhibition of types 1 and 2 5alpha-reductase and competitive binding to androgen receptors in prostatic cells. Here, the response of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF) in BPH tissue of patients treated with LSESr (320 mg/day for 3 months) is analyzed. METHODS: BPH samples were sectioned in periurethral, subcapsular, and intermediate regions: in each region T, DHT, and EGF were determined by radioimmunoassay after purification on celite columns or Sep-pak C18 cartridges. RESULTS: In the untreated group, T, DHT, and EGF presented the highest concentrations in the periurethral region (615 +/- 62 (SE) pg/g tissue, 7,317 +/- 551 pg/g tissue, and 20.9 +/- 3.3 ng/g tissue, respectively) with respect to the peripheral subcapsular region (425 +/- 45 pg/g tissue, 4,215 +/- 561 pg/g tissue, and 10.8 +/- 1.4 ng/g tissue, respectively). In the LSESr-treated group, a statistically significant reduction was observed, mainly in the periurethral region of DHT (2,363 +/- 553 pg/g tissue, P < 0.001) and EGF (6.98 +/- 2.48 ng/g tissue, P < 0.01), with increased T values (1,023 +/- 101 pg/g tissue, P < 0.001). CONCLUSIONS: The decrease of DHT and the rise of T in BPH tissue of patients treated with Permixon confirms the capacity of this drug to inhibit in vivo 5alpha-reductase in human pathological prostate. A marked decrease of EGF, associated with DHT reduction, was also observed. These biochemical effects, similar to those obtained with finasteride, are particularly evident in the periurethral region, whose enlargement is responsible for urinary obstruction, with respect to the subcapsular region. A possible speculation is that the preferential reduction of DHT and EGF content in the periurethral region is involved in the clinical improvement of the obstructive symptoms in BPH during LSESr therapy.

Androgen concentrations and their receptors in the periurethral region are higher than those of the subcapsular zone in benign prostatic hyperplasia (BPH).

Benign prostatic hyperplasia (BPH) is an androgen-dependent disease that initially develops in the inner prostate, where the highest concentrations of testosterone (T) and dihydrotestosterone (DHT) are found. In this study, we have evaluated the cytosolic androgen receptors (ARc), the nuclear androgen receptors (ARn), and the concentrations of T, DHT, and 3alpha-androstanediol (3alphaDiol) in BPH tissue to verify the existence of a possible correlation between androgens and their receptor concentrations. Prostatic samples, removed by suprapubic prostatectomy in 15 untreated patients, were sectioned in periurethral, intermediate, and subcapsular zones. Testosterone, DHT, and 3alphaDiol were evaluated by radioimmunoassay after extraction and purification on celite microcolumns, and ARc and ARn were evaluated by means of dextran-coated charcoal method. In total tissue, mean levels of DHT, T, and 3alphaDiol were 2,531+/-308, 260+/-36, and 403+/-35 pg/mg of DNA (mean+/-SE), respectively. Cytosolic androgen receptors, detectable in all cases, were 16+/-2.8 fmol/mg of protein (mean+/-SE), and ARn, detectable in 12 cases, were 108+/-15 fmol/mg of DNA (mean+/-SE). A linear correlation between DHT and 3alphaDiol, T and DHT, and 3alphaDiol and ARn was found. If the different regions are considered, the periurethral zone, site of the primitive BPH nodule, presents the highest levels of androgens and ARn with respect to the other regions. This relative hyperandrogenism may be responsible for the growth-promoting processes of this area, leading to urinary obstruction.

Insulin-like growth factor-I and -II in human benign prostatic hyperplasia: relationship with binding proteins 2 and 3 and androgens.

In prostatic tissue, androgen action may be mediated by growth factors such as insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for prostatic cells and modulate the stroma-epithelium interaction. IGF-binding proteins (IGFBPs) have an autocrine and/or paracrine role in regulating the local actions of the IGFs. In this study, testosterone, dihydrotestosterone (DHT), 3 alpha androstanediol (3 alpha diol), IGF-I, IGF-II, IGFBP2, and IGFBP3 concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue. Samples of prostate tissue were removed by suprapubic prostatectomy from twelve BPH patients. Androgen tissue levels were determined by radioimmunoassay after purification on celite microcolumns. IGF-I, IGFBP2, and IGFBP3 were measured by radioimmunoassay, and IGF-II by immunoradio metric assay, after acidification and chromatography on Sep-pak C18 Cartridges for IGF-I and IGF-II. Androgen concentrations, expressed in ng/g tissue (mean +/- SE), were 0.51 +/- 0.05 for testosterone, 5.3 +/- 0.16 for DHT, and 1.1 +/- 0.07 for 3 alpha diol. IGF-I, IGF-II, IGFBP2, and IGFBP3 levels were 24 +/- 3.7, 121 +/- 14 ng/g tissue and 0.44 +/- 0.05 and 1.2 +/- 0.17 micrograms/g tissue, respectively. No correlation between IGF-I, androgens, and IGFBPs was found. IGF-II was positively correlated with DHT (r = 0.78; p = 0.003) and 3 alpha diol (r = 0.66; p = 0.021) but not with IGFBPs. These data suggest that in BPH, DHT modulates the IGF system by increasing IGF-II without modifying IGFBPs. Therefore, the stroma-epithelium interaction, which plays an important role in prostatic growth, may be regulated by DHT through IGF-II.

Prevalent decrease of the EGF content in the periurethral zone of BPH tissue induced by treatment with finasteride or flutamide.

The aim of the present investigation is to verify whether treatment with Finasteride or Flutamide influences the regional distribution of testosterone (T), dihydrotestosterone (DHT), and epidermal growth factor (EGF) in benign prostatic hyperplasia (BPH) tissue. Thirty seven BPH patients were studied: 15 untreated, 9 treated with Flutamide (750 mg/day for 2 months), and 13 treated with Finasteride (5 mg/day for 3 months). Testosterone and DHT were evaluated by radioimmunoassay (RIA) after purification of the extracts on celite columns, and EGF was evaluated by RIA after purification on Sep-pak C18 cartridges in total tissue and in periurethral, subcapsular, and intermediate zone. In the untreated group, T, DHT, and EGF of the periurethral region are higher than those of the subcapsular zone (P < 0.01 for T and P < 0.001 for DHT and EGF). In the Flutamide group, DHT is not modified, T is increased (P = 0.045), and EGF is decreased in total tissue (P < 0.02) and in the periurethral zone (P < 0.01). In the Finasteride group, T is increased (P < 0.001), and DHT and EGF are decreased (P < 0.001), particularly in the periurethral zone. A positive linear correlation between DHT and EGF is observed in the Finasteride and in the untreated groups. In conclusion, in BPH the production of EGF is a DHT-dependent receptor-mediated function. The reduction of this growth factor during both treatments, associated with a fall of DHT in only the Finasteride group, is particularly evident in the periurethral zone. Since Finasteride reduces prostatic volume, mainly of the periurethral zone, we can speculate that DHT is responsible, either directly or indirectly through growth factors such as EGF for the enlargement of this region and thus responsible for urinary obstruction.