Routine Histopathologic Examination of Two Common Surgical Specimens—Appendix and Gallbladder: Is It a Waste of Expertise and Hospital Resources?

This study was undertaken to assess whether a routine histopathologic examination of two common surgical specimens (appendix and gallbladder) is needed and whether routine histopathologic examination has an impact on further management of patients. Histopathology reports of patients who had undergone appendicectomy and cholecystectomy, between 2006 and 2010, were analyzed retrospectively in the department of pathology of a tertiary care hospital. The case notes were retrieved in all cases of malignancies. Patients having a clinical diagnosis or suspicion of malignancy were excluded. The incidence and impact of unexpected pathologic diagnosis on postoperative management were noted. The study period included a total of 1,123 and 711 appendicectomy and cholecystectomy specimens, respectively. Fifteen (1.336 %) cases of appendicectomy specimens revealed incidental unexpected pathological diagnoses, which included tubercular appendicitis (n = 2), parasite (n = 8), neuroma (n = 1), carcinoid (n = 2), pseudomyxoma (n = 1), and adenocarcinoma (n = 1). About 88 % of such unexpected appendiceal findings had an impact on postoperative treatment. Unexpected pathologic gallbladder findings were found in 12 (1.68 %) of 711 cholecystectomy specimens. In 6 (0.84 %) cases, gallbladder cancer (GBC) was detected. Additional further management was required in 50 % of patients with unexpected gallbladder findings. Twenty of the total 1,834 specimens (1.090 %) had an impact on patient management or outcome and were not suspected on macroscopic examination at the time of surgery. These would have been missed had the specimens not been examined microscopically. The intraoperative diagnosis of the surgeon is therefore sometimes doubtful in detecting abnormalities of the appendix and gallbladder. This study supports the sending of all appendicectomy and cholecystectomy specimens for routine histopathological examination. Appendix and gallbladder should undergo routine histopathological examination. This is important in patients with advanced age and gallstones. Also, it is of great value in identifying unsuspected conditions which require further postoperative management. Selectively sending specimens for histopathological examination can result in reduced workload on the histopathology department without compromising patient safety.     

Vascular Endothelial-Targeted Therapy Combined with Cytotoxic Chemotherapy Induces Inflammatory Intratumoral Infiltrates and Inhibits Tumor Relapses after Surgery

Surgery is the most effective therapy for cancer in the United States, but disease still recurs in more than 40% of patients within 5 years after resection. Chemotherapy is given postoperatively to prevent relapses; however, this approach has had marginal success. After surgery, recurrent tumors depend on rapid neovascular proliferation to deliver nutrients and oxygen. Phosphatidylserine (PS) is exposed on the vascular endothelial cells in the tumor microenvironment but is notably absent on blood vessels in normal tissues. Thus, PS is an attractive target for cancer therapy after surgery. Syngeneic mice bearing TC1 lung cancer tumors were treated with mch1N11 (a novel mouse chimeric monoclonal antibody that targets PS), cisplatin (cis), or combination after surgery. Tumor relapses and disease progression were decreased 90% by combination therapy compared with a 50% response rate for cis alone (P = .02). Mice receiving postoperative mch1N11 had no wound-related complications or added systemic toxicity in comparison to control animals. Mechanistic studies demonstrated that the effects of mch1N11 were associated with a dense infiltration of inflammatory cells, particularly granulocytes. This strategy was independent of the adaptive immune system. Together, these data suggest that vascular-targeted strategies directed against exposed PS may be a powerful adjunct to postoperative chemotherapy in preventing relapses after cancer surgery.     

Remission in Rheumatoid Arthritis

With advancing therapeutic options, achieving a state of remission has become the treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission and what measures should be used to assess disease activity has remained a challenge. Multiple remission criteria have been devised and modified, all with different strengths and limitations. A consensus definition of remission will need to be achieved if we are to be able to evaluate outcomes of clinical trials and establish treatment targets for practice. Remission defined as the complete absence of disease currently may not be a realistic therapeutic goal.     

Effect of Anchorage on the Accuracy of Fit in Removable Partial Denture Framework

Purpose: This study evaluated the effect of anchorage on the accuracy of fit in removable partial denture framework. Materials and Methods: Twenty‐four partially edentulous maxillary refractory casts were duplicated from a machine‐milled metal cast. Twelve of these were included in the test group, which had the provision for anchorage in the refractory cast, and the remaining 12 were taken as control group, which did not have provision for anchorage. Identical wax patterns for the maxillary strap major connector were invested and cast in cobalt chromium alloy. The accuracy of fit of the cast partial major connector frameworks were measured at two selected points using a profile projector. The resultant data were analyzed using student's t‐test and unpaired t‐test. Results: Student's t‐test showed statistically significant improvement in the fit of the major connectors of the test group at point A (p= 0.0003) and P (p= 0.0074). Unpaired t‐test was performed for the control and test group. The results of the unpaired t‐test for the control group exhibited a greater gap discrepancy (0.44 ± 0.20 mm) than for the test group at point A (0.16 ± 0.10 mm). Similarly, the gap was more at Point P for the specimens in the control group (0.65 ± 0.10 mm) than the test group (0.42 ± 0.24 mm). Conclusion: Within the limitations of the study it is concluded that the accuracy of fit of the palatal major connector was significantly better in the test group than the control group, with 0.1% level of significance at point P. The accuracy was significantly improved in both groups at point A by 1% level of confidence.     

Laboratory control of oral anticoagulant treatment by the INR system in patients with the antiphospholipid syndrome and lupus anticoagulant. Results of a collaborative study involving nine commercial thromboplastins

Because of the variable responsiveness of thromboplastins to lupus anticoagulants (LA), concerns have been raised about the validity of the prothrombin time-International Normalized Ratio (PT-INR) in monitoring oral anticoagulant treatment in patients with the antiphospholipid syndrome (APS) and LA. To date, few studies have been performed, numbers of patients investigated are relatively small and results are conflicting. We report on a multicentre study organized to investigate further this clinically relevant issue. Each of nine thrombosis centres was asked to collect plasma samples from patients with APS who were on oral anticoagulants (cases) and patients without APS who were on oral anticoagulants (controls). Nine thromboplastins (three human recombinant, one from human placenta and five from rabbit brain) were calibrated at the co-ordinating centre according to World Health Organization guidelines. Measurements of the INR and factor X amidolytic activity for all frozen plasmas were performed centrally. The numbers of patients investigated were 58 cases and 57 controls. Between-reagent variability of the INR was higher in cases [coefficient of variation (CV) = 12.4%] than in controls (CV = 6.7%), but this was because of one of the thromboplastins only (Thromborel R, human recombinant), which measured considerably higher INR values than the others in cases but not in controls. In conclusion, our data indicate that LA interference on the PT-INR measured with the majority of commercial thromboplastins is not enough to cause concern if insensitive thromboplastins, properly calibrated to assign them an instrument-specific International Sensitivity Index are used. New thromboplastins, especially those made of relipidated tissue factor, should be checked for their responsiveness to LA before they are used to monitor oral anticoagulant treatment in patients with APS.     

Benign Signet Ring Cell Change with Multilayering in the Gallbladder Mucosa: A Case Report

We describe a case of benign signet ring cell change in the gallbladder mucosa. On histopathological examination of H&E-stained sections, the gallbladder epithelium showed multilayering. The epithelial cells were large, columnar to polygonal with a small round basal or eccentric nucleus and vacuolated cytoplasm, giving them a signet ring appearance. There was no nuclear atypia, hyperchromatism or mitotic activity. The cells showed uniform positivity with mucicarmine, PAS and Alcian blue stains. The cytoplasmic vacuolations were negative for fat stains (Oil red O and Sudan IV). On immunohistochemistry, the cells showed positivity with antibodies for pancytokeratin (PCK) and epithelial membrane antigen (EMA). A diagnosis of benign signet ring cell change with multilayering in the gall bladder mucosa was made. Thoroughly reviewing the literature, we found only one case of benign signet ring cell aggregates in the gallbladder mucosa documented earlier. The lesion is hereby reported because of the unique histomorphology and the diagnostic dilemma which can occur as a malignant change in situ has to be excluded.     

A strategy to achieve donor-specific hyporesponsiveness in cadaver renal allograft recipients by donor haematopoietic stem cell transplantation into the thymus and periphery.

INTRODUCTION: We designed a prospective, randomized clinical trial to evaluate the immune response to thymic and peripheral infusions of donor haematopoietic stem cells (HSCs) to create tolerance in recipients of cadaver renal allografts. METHOD: We divided 24 patients into two equal groups. For group A, 350 ml of unfractionated bone marrow (BM) was aspirated from the anterior iliac crests of donor cadavers. A 2 ml aliquot of concentrated marrow was infused into the thymus of the subject and 100 ml into the BM before surgery; the remaining 250 ml was infused peripherally post-transplantation. The mean nucleated cell count inoculated into the thymus was 3.3 x 10(4) cells/cm(3) and into the periphery 8.6 x 10(7) cells/kg body weight. Group B (controls) underwent renal transplantation directly. Recipients were lymphocytotoxicity cross-match negative in both groups. Group A received low dose prednisolone and cyclosporin; controls also received azathioprine. RESULTS: Over a mean follow-up of 703 days for both groups, group A had significantly better graft function with minimum acute rejection episodes or cytomegalovirus (CMV) infections, a mean serum creatinine (SCr) of 1.23 mg/dl and no graft or patient loss. Group B, with a mean SCr of 2.19 mg/dl had three patients with single acute rejection episodes, two of whom died following uncontrolled rejection-associated infections. The third patient maintained an SCr of 2.5 mg%. Actuarial graft survival was 87.5% in controls at the end of 2 years compared with group A with 100% graft survival at the end of 2 years. CONCLUSION: This novel approach of introducing unfractionated HSCs into the thymus and periphery to create tolerance is safe and efficacious and gives significantly better graft function, minimum acute rejection and no CMV disease with monotherapy.