Duodenocolic fistula healing by pentadecapeptide BPC 157 in rats. A cytoprotection viewpoint.

Using duodenocolic fistula in rats, this study attempts to highlight the particular cytoprotection aspects of the healing of fistulas and therapy potential of the stable gastric pentadecapeptide BPC 157, a cytoprotection mediator (i.e. upgrading minor vessels to induce healing at both fistula's sides). Upon duodenocolic fistula creation (two 'perforated' lesions put together) (assessed at 3, 6, 9, 12, and 15 min), BPC 157, given locally at the fistula, or intragastrically (10 µg/kg, 10 ng/kg), rapidly induces vessel 'recruitment', 'running' toward the defect, simultaneously at duodenum and colon, providing numerous collaterals and branching. The mRNA expression studies done at that time provided strongly elevated (nitric oxide synthase 2) and decreased (cyclooxygenase-2, vascular endothelial growth factor A, nitric oxide synthase (NOS)-1, NOS-3, nuclear factor-kappa-B-activating protein) gene expression. As therapy, rats with duodenocolic fistulas, received BPC 157 10 µg/kg, 10 ng/kg, per-orally, in drinking water till sacrifice, or alternatively, intraperitoneally, first application at 30 min after surgery, last at 24 h before sacrifice, at day 1, 3, 7, 14, 21, and 28. Controls exhibited both defects persisting, continuous fistula leakage, diarrhea, continuous weight loss, advanced adhesion formation and intestinal obstruction. Contrary, all BPC 157-treated rats have closed both defects, duodenal and colonic, no fistula leakage (finally, maximal instilled volume corresponds to healthy rats), no cachexia, the same weight as before surgery, no diarrhea, markedly less adhesion formation and intestinal passage obstruction. Thus, BPC 157 regimens resolve the duodenal/colon lesions and duodenocolic fistulas in rats, and rapid vessels recovery appears as the essential point in the implementation of the cytoprotection concept in the fistula therapy.

Neoadjuvant chemotherapy in patients with breast cancer: Does response in the breast predict axillary node response?

INTRODUCTION: Determining the extent of residual disease in the breast and axilla following neoadjuvant chemotherapy (NACT) is vital for surgical planning. Traditionally patients with incomplete radiological response in the breast after NACT undergo axillary node clearance, regardless of axillary clinical and radiological response. The aim of this study was to determine whether radiological and/or pathological response in the breast to NACT were predictive of axillary response. MATERIALS AND METHODS: A retrospective cohort study of patients with operable breast cancer with histologically proven axillary lymph node involvement who received NACT and underwent definitive surgical treatment between 1/1/2016 and 31/12/2018 were included. All had MRI and/or US of the breast and axilla before, mid-treatment and at the end of NACT. RESULTS: The 83 patients had a median age of 50 years (range 25-77). MRI had a positive predictive value (PPV) of 52.6% and negative predictive value (NPV) of 81.8% for breast pathological complete response (pCR). For axillary pCR, US had a PPV of 60.0% and NPV of 89.6%. Only 71% of patients had radiological concordance; 15.9% had radiological complete response (rCR) in breast and axilla whilst 55.1% had neither breast nor axillary rCR. 85.6% of patients had pathological concordance (20.5% with breast and axillary pCR: 65.1% with residual disease in both). CONCLUSION: Radiological and pathological response in the breast to NACT does not accurately predict axillary response. The axilla and the breast should be viewed and assessed as two separate entities for treatment plans.

Keeping children safe: a model for predicting families at risk for recurrent childhood injuries.

OBJECTIVE: Existing research on recurrent unintentional injury (UI) focuses on the individual child rather than family risks. This study developed a statistical model for identifying families at highest risk, for potential use in targeting public health interventions. STUDY DESIGN: A retrospective birth cohort study of hospital and emergency room (ER) medical records of children born in Ziv hospital between 2005 and 2012, attending ER for UI between 2005 and 2015, was conducted. METHODS: Using national IDs, we assigned children to mothers and created the family entity. Data were divided into two time periods. Negative binomial regression was used to examine predictive factors in the first period for recurrent child UI in the second period. Sensitivity analyses were conducted to examine the model's robustness. RESULTS: Eight predictive factors for child injury (P < 0.05) were found: male gender, the number of UI visits, the number of illness visits, age 36-59 months, birth weight <1500 g, maternal ER visits, siblings' UI visits, and the number of younger siblings. Some predictive factors are documented in the literature; others are novel. Five were significant in all sensitivity analyses. CONCLUSIONS: These factors can assist in predicting risk for a child's repeat UI and family's cumulative UI risk. The model may offer a valuable and novel approach to targeting interventions for families at highest risk.

An endogeous defensive concept, renewed cytoprotection/adaptive cytoprotection: intra(per)-oral/intragastric strong alcohol in rat. Involvement of pentadecapeptide BPC 157 and nitric oxide system.

With intra(per)-oral strong alcohol application at the tongue, swallowed, we renewed Robert's stomach cytoprotection/adaptive cytoprotection concept. We assessed strong (96%) alcohol-induced severe or minute lesions in stomach, tongue-esophagus-stomach-duodenum lesions, and sphincter pressure (lower esophageal and pyloric) upon administration intragastrically (at 1 h) or intra(per)-orally at the tongue, and swallowed (at 1, 5, 15, 30 min; and 1, 2, 24 h). The assessment also included combined administrations (intra(per)-oral at the tongue, swallowed and intragastric (at 1 h)). Immediate post-alcohol intraperitoneal medication (mg/kg) was the stable gastric pentadecapeptide BPC 157 (0.01, 0.00001; a Robert's cytoprotection mediator; with a therapeutic effect), NOS-blocker L-NAME (5), and NOS-substrate L-arginine (100 mg), (NO-system involvement). After intragastric strong alcohol administration, severe stomach ulcerations appeared along with widespread tongue, esophagus, duodenum redness, and minimal sphincter pressures. By contrast, a particular syndrome (immediate overlapping of cytoprotection/adaptive cytoprotection) (minute gastric lesion or largely attenuated hemorrhagic ulceration, tongue affected, minute esophageal and duodenal lesions, but with intact mucosa; sphincters pressures lowered) appeared after intra(per)-oral administration (1 min-24 h) as well as after combined administrations (intra(per)-oral + intragastric). BPC 157 apparently cured all alcohol-lesions, amplified the spontaneously initiated strong mucosal beneficial effect, rescued sphincter pressures; NO-agents (L-arginine (slight mucosal amelioration) and L-NAME (aggravation)) showed NO-system involvement, but no comparable effects on dropped sphincters pressures. In conclusion, minute gastric lesions (with oral application of strong alcohol at the tongue and swallowed, without, or with intragastric application of strong alcohol) renew and revise Robert's stomach cytoprotection/adaptive cytoprotection concept. The tongue becomes a new initial target, resulting in spontaneous reversal of strong alcohol-stomach lesions. BPC 157 therapy functions also within the redirected complexity of Robert's stomach cytoprotection/adaptive cytoprotection concept.

Live birth after transfer of vitrified-warmed blastocyst derived from ICSI with frozen-thawed sperm: case report.

OBJECTIVE: A live birth after transfer of vitrified-warmed blastocyst derived from intracytoplasmic sperm injection (ICSI) with frozen-thawed sperm of a male cancer patient is described. MATERIALS AND METHODS: A case report from a tertiary center for assisted reproductive technologies. The 35-year-old male patient had been diagnosed with testicular tumor nine years ago. He had unilateral orchiectomy operation after the diagnosis. Four years after the first operation, he was diagnosed with another testicular tumor in the other testis. He admitted to our center with the demand of sperm preservation before the second surgery. The sperm samples were cryopreserved and stored in liquid nitrogen until required. The patient had no chemotherapy or radiotherapy after the operations. After he completed his oncologic follow up, ICSI was decided with his frozen samples. Although the couple failed to conceive with the fresh cycle, the remaining embryos were frozen and revealed a pregnancy in the subsequent frozen-thawed cycle. RESULTS: A healthy female infant with a birth weight of 3,700 g was born by cesarean section at 38th weeks of the gestation. CONCLUSION: Giving detailed information about fertility-saving management in male patients is important in those who wish to bear children. However, both the patients and physicians should be cautious that preservation should be performed before surgery and/or adjuvant therapy. In this respect, assited reproductive technology (ART) and related facilities yield chance of pregnancy in such population.

Sentinel lymph node localization with contrast-enhanced ultrasound and an I-125 seed: an ideal prospective development study.

INTRODUCTION: Our aim was to evaluate the development of microbubble-enhanced sentinel lymph node (SLN) localization with placement of an I-125 seed in breast cancer patients as a potential alternative for SLN localization with nanocolloid. The study is conducted and reported following the IDEAL recommendations for evaluation of a new technique at Stage 2a (Prospective Development Study). METHODS: Fourteen consecutive patients with 15 lesions underwent microbubble-enhanced SLN localization with placement of an I-125 seed after the standard SLN localization (nanocolloid). We placed an I-125 seed within or near the SLN following its identification using intradermally injected microbubbles. The SLN was excised guided by nanocolloid and the SLN containing the I-125 seed was searched for. All technical modifications are described and standardized outcomes measured. RESULTS: Twelve (80%) microbubble procedures with I-125 seed placements were technically successful. In three cases no microbubble-enhancing lymph node could be detected. Intraoperatively, we found nine I-125 seeds within 0.5 cm of the nanocolloid confirmed SLN. One I-125 seed was found next to a non-SLN and two I-125 seeds were not near any lymph node. Overall, the procedure was successful in 60% (9 out of 15) of the cases. CONCLUSION: Given the low success rate, we conclude that microbubble-enhanced SLN is not a viable alternative to the standard SLN procedure. Modifications to this technique did not improve its performance. Planned study (NTR3690 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3690) was stopped early due to this conclusion and results reported in order to provide a full and transparent record of the evolution of technique.

Can combination of Day 3 and Day 5 embryo morphology be useful to predict pregnancy in in-vitro fertilization cycles?

OBJECTIVE: To determine whether embryos having all top qualified both on Day 3 and Day 5 have higher pregnancy rates than the oth- ers. MATERIALS AND METHODS: The study included 143 consecutive cycles were recruited in which Day 5 embryo transfer was available. Cleavage stage embryos were graded according to 1 to 4 scoring system, based on fragmentation, cell symmetry, and blastomere num- ber. Among cleavage stage embryos, Grade 1 and Grade 2a/2b were further stratified as 'top quality' embryos to be transferred, others were defined as control group. Blastocyst stage embryos were graded from 1 to 6 according to intracellular mass (ICM) and trophec- toderm (TE). Day 5 fresh embryo transfer was performed in all cases using soft catheter. Positive pregnancy test was accepted when serum beta-human chorionic gonadotrophin (1-hCG) exceeded 20 mIU/ml. RESULTS: On the cleavage stage, top quality embryo was available in 47 of 143(32.9%) cases. Of the 47 embryos, the number of cases reaching any Grade 4, 3 quality, and early blastocyst on Day 5 were 22 (46.8%), 15 (31.9%), and 10 (21.3%). The respective figures on the control group (n = 96) were 33 (34.4%), 37 (38.5%), and 26 (27.1%) (p > 0.05). The pregnancy rates were also similar. CONCLUSION: All top qualified embryos both on Day 3 and 5 did not reveal higher pregnancy rate than the others.

Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound.

BACKGROUND: In patients with breast cancer, grey-scale ultrasound often fails to identify lymph node (LN) metastases. We aimed to validate the technique of contrast-enhanced ultrasound (CEUS) as a test to identify sentinel lymph node (SLN) metastases and reduce the numbers of patients requiring a completion axillary node clearance (ANC). METHODS: 371 patients with breast cancer and a normal axillary ultrasound were recruited. Patients received periareolar intra-dermal injection of microbubble contrast agent. Breast lymphatics were visualised by CEUS and followed to identify and biopsy axillary SLN. Patients then underwent standard tumour excision and either SLN excision (benign biopsy) or axillary clearance (malignant biopsy) with subsequent histopathological analysis. RESULTS: The technique failed in 46 patients, 6 patients had indeterminate biopsy results and 24 patients were excluded. In 295 patients with a conclusive SLN biopsy, the sensitivity of the technique was 61% and specificity 100%. Given a benign SLN biopsy result, the post-test probability that a patient had SLN metastases was 8%. 35 patients were found to have SLN metastases and had a primary ANC (29 macrometastases and 6 micrometastases/ITC). There were 22 false negative results (10 macrometastases and 12 micrometastases). Macrometastases in core biopsy specimens correlated with LN macrometastases on surgical excision. CONCLUSION: Pre-operative biopsy of SLN reduced the numbers of patients requiring completion ANC. Despite the low sensitivity, only 22 patients (8%) with a benign SLN biopsy were subsequently found to have LN metastases. Without the confirmation of macrometastases on core biopsy specimens, patients with micrometastases/ITC may be inadvertently selected for primary ANC.

Sentinel node identification using microbubbles and contrast-enhanced ultrasonography.

Sentinel lymph node (SLN) biopsy has become the recommended method for surgical staging of the axilla in patients with breast cancer. Grey-scale axillary ultrasonography (US) combined with US-guided biopsy is a widely used preoperative staging procedure but has limited sensitivity. US contrast agent "microbubbles", when injected intradermally, have been shown to have the potential to enter the breast lymphatics, travel rapidly to the axilla, and visualize the putative SLNs. This review illustrates the SLN identification technique using intradermal injection of microbubbles and contrast-enhanced US. The injection method, lymphatic visualization techniques, grey-scale and contrast-enhanced US images of the putative SLNs are reviewed and exemplified.

Preoperative localization of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasonography in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard procedure for axillary staging in early breast cancer. Lymphatic imaging after intraparenchymal microbubble injection has been reported in animal models. The aim of this study was to identify and localize SLNs before surgery by contrast-enhanced ultrasonography after intradermal injection of microbubbles in patients with breast cancer. METHODS: Fifty-four consecutive, consenting patients with primary breast cancer were recruited. Patients received a periareolar intradermal injection of microbubble contrast agent. Breast lymphatics were visualized by ultrasonography and followed to identify putative axillary SLNs. A guidewire was deployed to localize the SLN. The next day, patients underwent standard tumour excision and SLN biopsy. RESULTS: SLNs were identified and guidewires inserted in 48 patients. In these patients operative findings confirmed that the wired lymph nodes were SLNs. The sensitivity of SLN detection, compared with radioisotope and blue dye, was 89 per cent. Five patients were found to have metastases in SLNs. In these patients the SLNs were identified correctly and localized before surgery with guidewires. CONCLUSION: SLNs may be identified and localized before surgery using contrast-enhanced ultrasonography after injection of microbubbles.

Scar formation after stereotactic vacuum-assisted core biopsy of benign breast lesions.

AIM: To evaluate scar formation of impalpable breast lesions with benign histological outcome using stereotactic 11-gauge vacuum-assisted core biopsy (VACB). MATERIALS AND METHODS: Two hundred and ten lesions with benign histology for which follow-up mammograms were available, were assessed for scar formation at the biopsy site. All biopsies were performed using stereotactic VACB with 11-gauge needle. The incidence of post-biopsy scar formation and the number of specimens removed were determined. RESULTS: In 4.3% (9/210) of the lesions for which a biopsy was performed with 11-gauge directional vacuum-assisted technique, the follow-up mammogram revealed a scar formation. Of these, six were minimal scars, two were moderate scars and one was a marked scar. Minimal and moderate scars were diagnosed on imaging only. However, the case with marked scar formation required tissue diagnosis to rule out malignancy. CONCLUSION: Although uncommon, scar formation can be seen in the follow-up mammograms after percutaneous breast biopsies. It is important that the radiologist interpreting follow-up mammograms is aware of the features of this lesion and its relationship to the biopsy procedure.

Unusually large cisterna chyli: US and MRI findings.

We report a rare appearance of cisterna chyli appearing as a giant cystic structure on routine abdominal ultrasonography (US). Diagnosis was established with color Doppler US and after magnetic resonance imaging. This report describes an unusual appearance of the cisterna chyli that radiologists should be familiar with, especially on the routine conventional gray-scale US to avoid mistaking it for a pathologic condition.

Audit of local recurrence rates following 'ultra'-conservative surgery for invasive breast cancer--a boost to the breast?

BACKGROUND: Conservative breast surgery with postoperative radiotherapy and appropriate systemic therapy is associated with similar outcomes when compared with mastectomy. The reported 5 year local recurrence rate varies between 3% and 15%. We prefer a more conservative 'complete' local excision rather than 'wide' local excision combined with post-operative radical radiotherapy and tumour bed boost with the aim of achieving optimal cosmesis. AIMS: Our review was undertaken to assess whether or not this 'ultra' conservative approach was compromising long-term local control. METHODS: Case notes and pathology reports of patients who underwent conservative surgery for breast cancer from January 1983 to February 2001 were accessed for this audit. Patient demographic data and tumour characteristics were noted. The primary outcome data were the number of local recurrences following invasive breast cancer at 5 and 10 years and the distance from the tumour to the closest margin of excision. RESULTS: At 5 and 10 years there were 16/451 and 5/124 local recurrences, with a local recurrence rate of 3.5% (95% CI, 1.7-4.7%) and 4.1% (95% CI, 0.47-6.5%), respectively. Complete data with regards to the closest histological margin of excision were available in 423 patients. One hundred and sixty-five patients (39%) had their tumours excised with a distance of less than 1 mm to the closest margin. Nearly, all tumours (97.8%) were excised with the distance to the closest margin less than 1 cm and 81% with 5 mm or less. CONCLUSION: It is possible to achieve low local recurrence rates after very conservative surgery for breast cancer when this is combined with radical radiotherapy and an additional tumour bed boost.

Sinistral portal hypertension; imaging findings and endovascular therapy.

Sinistral portal hypertension, a rare and localized form of portal hypertension, is the result of splenic vein thrombosis or obstruction and may cause gastrointestinal hemorrhages from the esophageal and gastric varices. This report presents two cases (69- and 10-year-old females) of bleeding gastric varices. The patients were diagnosed as having sinistral portal hypertension. Splenic artery embolization was performed in both patients to overcome intractable bleeding, and the clinical outcome was good.

Colorectal carcinoma: radiological diagnosis and staging.

Colorectal carcinomas are the most common gastrointestinal tract tumors. 50-60% of the colorectal carcinomas originate in rectum and sigmoid colon. The new developments in imaging modalities have brought improvements in therapeutic aspects. The survival rates in these patients depend on the tumor penetration and the presence of regional lymph node or distant metastasis. The recurrence rates have decreased with the new operation techniques and preoperative radiotherapy, thus increasing the importance of accurate tumor staging. Double contrast barium enema studies enable the diagnosis while staging and follow-up is best done by topographic imaging techniques.

A comparison of aspiration cytology and core needle biopsy in the evaluation of breast lesions.

BACKGROUND: Several arguments are used for choosing either fine-needle aspiration cytology (FNAC) or core needle biopsy (CNB) in the evaluation of breast lesions. Comparison of published data on both methods is complicated by differences in study design, calculations, and operator experience. The objective of this study was to make a direct comparison of both methods. METHODS: In 286 breast lesions (cysts and microcalcifications without a soft tissue mass excluded), both ultrasound-guided FNAC and CNB were performed in the same session by the same operator. Histologic follow-up was collected, and for those lesions that were not excised the results of the most recent mammography was used. A combination of the findings of both FNAC and CNB were evaluated. RESULTS: Core needle biopsy and FNAC do equally well for sensitivity (88% vs. 92%), positive predictive value for malignancy (99% vs. 100%), and inadequate rate (7% vs. 7%). However, statistical differences are found for the specificity (CNB, 90%; FNAC, 82%). In addition, differences are found in the positive predictive value of both suspicious (CNB, 100%; FNAC, 78%) and atypia (CNB, 80%; FNAC, 18%) and for the suspicious rate (CNB, 5%; FNAC, 13%) reflecting difficulties in interpreting some FNACs. Combining the findings of both FNAC and CNB results in an increase in absolute sensitivity, a decrease in the positive predictive value of atypia compared with FNAC and CNB per se, and a decrease in the inadequate rate for cancers. CONCLUSIONS: For the lesions selected in this study, FNAC and CNB are comparable for most parameters, but CNB has a higher specificity and lower suspicious rate. Combining results of FNAC and CNB leads to an increase in absolute sensitivity without affecting specificity and a decrease in the inadequate rate for cancers.

[Fungus-induced arthritis caused by Scedosporium apiospermum (Pseudallescheria Boydii)]. / Uber eine Pilz-induzierte Arthritis durch Scedosporium apiospermum (Pseudoallescheria Boydii).

Scedosporium (monosporium) apiospermum is the most common causative agent of maduro mycosis. Recent research reports claim that this fungus can also induce arthritis. We report on the disease in a woman from a rural area who was admitted to our clinic because of arthritis symptoms. We were able to detect Scedosporium apiospermum, i.e., it was probably a fungus-induced arthritis which had developed after an intraarticular steroid injection.