Bipolar Hemiarthroplasty and Parathyroidectomy at the Same Setting for Fragility Fractures Secondary to Renal Bone Disease.

BACKGROUND: From 1980s to the new millennium, the number of patients surviving with end stage renal disease (ESRD) has increased by 3 fold. This is driven by early detection of primordial and primary risk factors, state of the art renal replacement therapy and ease of public access to healthcare. Renal osteodystrophy (RO) is a metabolic bone disease causing significant morbidity in patients with ESRD, in particular fragility fractures. In this case series, we present the surgical management of 3 ESRD patients with pathological fractures of the neck of femur (NOF) and surgical treatment (parathyroidectomy) of tertiary hyperparathyroidism of ESRD patients in the same surgical setting. Up to date there has been no reports on bipolar hemiarthroplasty and total parathyroidectomy implemented in the same operative setting. METHODS: We present 3 cases, 2 males and a female with an average age of 48 years. All patients presented with no trauma or minimal trauma. With high index of suspicion and after confirming the diagnosis with advanced imaging, the patients underwent cemented modular hemiarthroplasty with posterior approach. Parathyroidectomy was sequentially performed to address the tertiary hyperparathyroidism at the same setting. We followed them for 48 months. RESULTS: At 48-month follow up, all the patients were at their pre-morbid ambulatory status and there were no major complications. They did not need any revision surgery or re-operation either for the hemiarthroplasty surgery or the parathyroidectomy during the follow up period. CONCLUSION: To avoid diagnostic pitfalls in this group of patients we recommend MRIs of both hips in patients complaining of unilateral hip pain even when the roentgenograms are clear of fractures. Total parathyroidectomy at the same setting with the bipolar hemi-arthroplasty is a safe combination. This reduces the anaesthesia risk, the recovery time as well as the equilibrium time for calcium homeostasis.

Development of an enhanced acute care surgery service in response to the COVID-19 global pandemic.

BACKGROUND: As the COVID-19 pandemic sweeps across the world, healthcare departments must adapt to meet the challenges of service provision and staff/patient protection. Unlike elective surgery, acute care surgery (ACS) workloads cannot be artificially reduced providing a unique challenge for administrators to balance healthcare resources between the COVID-19 surge and regular patient admissions. METHODS: An enhanced ACS (eACS) model of care is described with the aim of limiting COVID-19 healthcare worker and patient cross-infection as well as providing 24/7 management of emergency general surgical (GS) and trauma patients. The eACS service comprised 5 independent teams covering a rolling 1:5 24-hr call. Attempts to completely separate eACS teams and patients from the elective side were made. The service was compared to the existing ACS service in terms of clinical and efficiency outcomes. Finally, a survey of staff attitudes towards these changes, concerns regarding COVID-19 and psychological well-being was assessed. RESULTS: There were no staff/patient COVID-19 cross-infections. Compared to the ACS service, eACS patients had reduced overall length of stay (2-days), time spent in the Emergency Room (46 min) and time from surgery to discharge (2.4-hours). The eACS model of care saved financial resources and bed-days for the organisation. The changes were well received by team-members who also felt that their safety was prioritised. CONCLUSION: In healthcare systems not overwhelmed by COVID-19, an eACS model may assist in preserving psychological well-being for healthcare staff whilst providing 24/7 care for emergency GS and trauma patients.

Randomized control trial comparing an Alvarado Score-based management algorithm and current best practice in the evaluation of suspected appendicitis.

BACKGROUND: An objective algorithm for the management of suspected appendicitis guided by the Alvarado Score had previously been proposed. This algorithm was expected to reduce computed tomography (CT) utilization without compromising the negative appendectomy rate. This study attempts to validate the proposed algorithm in a randomized control trial. METHODS: A randomized control trial comparing the management of suspected acute appendicitis using the proposed algorithm compared to current best practice, with the rate of CT utilization as the primary outcome of interest. Secondary outcomes included the percentage of missed diagnosis, negative appendectomies, length of stay in days, and overall cost of stay in dollars. RESULTS: One hundred sixty patients were randomized. Characteristics such as age, ethnic group, American Society of Anesthesiologist score, white cell count, and symptom duration were similar between the two groups. The overall CT utilization rate of the intervention arm and the usual care arm were similar (93.7% vs 92.5%, p = 0.999). There were no differences in terms of negative appendectomy rate, length of stay, and cost of stay between the intervention arm as compared to the usual care arm (p = 0.926, p = 0.705, and p = 0.886, respectively). Among patients evaluated with CT, 75% (112 out of 149) revealed diagnoses for the presenting symptoms. CONCLUSION: The proposed AS-based management algorithm did not reduce the CT utilization rate. Outcomes such as missed diagnoses, negative appendectomy rates, length of stay, and cost of stay were also largely similar. CT utilization was prevalent as 93% of the study cohort was evaluated by CT scan. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov (NCT03324165, Registered October 27 2017).

NOR-1 distinguishes acinic cell carcinoma from its mimics on fine-needle aspiration biopsy specimens.

Acinic cell carcinoma of the salivary gland (ACC-SG) is characterized by a recurrent chromosomal rearrangement (t(4; 9)(q13; q31)) that upregulates the transcription factor NR4A3. Studies conducted on formalin-fixed paraffin-embedded (FFPE) tissue have found that nuclear expression of a monoclonal antibody NR4A3 (NOR-1) is a sensitive and specific diagnostic marker for ACC-SG. The aims of this study were to evaluate the performance of the NOR-1 antibody and to compare its utility in separating ACC-SG from its mimics on cytology cell block specimens. Cell blocks were obtained from 70 fine-needle aspiration specimens from multiple institutional archives over a 7-year period (2013-2019). These included 10 cases of conventional low-grade ACC-SG, 1 case of dedifferentiated high-grade ACC-SG, and 59 cases of non-ACC-SG. An automated immunohistochemistry system (Bond-III, Leica) was used for the detection of NR4A3, using the commercially available antibody NOR-1 (sc-393902 [H-7], Santa Cruz Biotechnology Inc.). Optimization of the antibody on the cell blocks was successfully completed by increasing the titer from 1:100 (suggested titer for FFPE specimens) to 1:30. Distinct nuclear reactivity was observed in all 11 cases of ACC-SG (10 of 11 with 3+ diffuse nuclear positivity and 1 case with 2+ focal reactivity). Expression of NR4A3 was absent in all non-ACC-SG cases in the cell blocks. Application of the NOR-1 immunohistochemical staining in fine-needle aspirates of salivary gland tumors for which ACC-SG is a diagnostic consideration successfully distinguishes ACC-SG from its cytologic mimics and provides an early opportunity for oncologic intervention.

Hungry bone syndrome after parathyroidectomy in end-stage renal disease patients: review of an alkaline phosphatase-based treatment protocol.

AIM: Hyperparathyroidism in chronic kidney disease-mineral and bone disorder is associated with significant morbidity and mortality. Parathyroidectomy is widely carried out as treatment despite complications such as hypocalcaemia post-surgery. Our centre has been using an ALP-based protocol to replace calcium postoperatively to prevent hypocalcaemia. We aim to describe and audit our calcium replacement protocol post-parathyroidectomy METHODS: We, retrospectively, analyse 167 end-stage kidney disease patients who had parathyroidectomy with auto-implantation in Singapore General Hospital between January 2008 and December 2013. Their calcium replacement postoperatively was initiated upon patient arrival back in ward on the same day of surgery based on their pre-op ALP prior to occurrence of hypocalcaemia. Patient demographics, surgical and laboratory parameters were reviewed from medical records. Changes in calcium postoperatively were reported to look for incidence of calcium derangement. RESULTS: Mean calcium levels between pre-operation day and post-operation day 7 ranged from 2.31 to 2.70 mmol/L. Decline in serum calcium was common in all patients prior to starting calcium replacement. Eighteen patients (10.9%) experienced hypocalcaemia immediately post-operation prior to commencement of IV calcium replacement. Patients with immediate post-operation hypocalcaemia had lower pre-operation calcium but higher pre-operation alkaline phosphatase (ALP) and pre-operation intact parathyroid hormone. Hypercalcaemia is common likely from aggressive IV calcium replacement using the protocol. The average length of stay for patients prior to calcium stabilization and discharge was 9 days. CONCLUSION: Implementation of an ALP-based prophylactic calcium replacement protocol with daily serum calcium monitoring can ameliorate severe hypocalcaemia post-parathyroidectomy.

Comparing the Utility and Surgical Outcomes of Harmonic Focus Ultrasonic Scalpel with Ligasure Small Jaw Bipolar Device in Thyroidectomies: A Prospective Randomized Controlled Trial.

BACKGROUND: Ultrasonic or bipolar radiofrequency energy devices are routinely used for dissection and hemostasis during thyroidectomy. We report a single-center, prospective, randomized controlled trial comparing the utility and outcomes of Harmonic Focus, an ultrasonic coagulating shear device (UCSD), versus Ligasure Small Jaw, an electrothermal bipolar vessel sealer (EBVS) in thyroidectomy (NCT01765686). METHODS: Between December 2012 to January 2016, eligible patients were randomized to undergo hemithyroidectomy using either a UCSD or an EBVS. The primary outcome was duration of surgery. Secondary outcomes included blood loss, postoperative complications, ease of device use, ease of device set-up, vocal cord function, postoperative wound drainage, pain score, and adverse events. RESULTS: Of 110 patients assessed for eligibility, 100 were randomly allocated (UCSD: 49 patients; EBVS: 51 patients) and analyzed by intention-to-treat. There were no differences in specimen delivery time, total duration of surgery, wound drainage, and adverse events between the two groups. The UCSD group had a greater proportion of patients with higher postoperative pain scores in the first 72 h (8.1% vs. 2.0%, p = 0.043). Surgeons reported greater ease of use for the UCSD (49% vs. 27%; p = 0.005), while operating room staff favored the EBVS (60% vs. 33%, p = 0.005). CONCLUSIONS: Energy devices are equally effective in reducing thyroidectomy operative times, with no differences in the duration of surgery, drainage, or adverse events. Use of the UCSD was associated with higher postoperative pain scores, but was favored by the surgeons, likely due to the ability to perform fine dissection with the device itself.

Effect of Hydrochloric Acid Decalcification on Expression Pattern of Prognostic Markers in Invasive Breast Carcinomas.

CONTEXT: In the United States, it is estimated that 100,000 people are living with metastatic breast cancer (BC) with bone representing the most common site of involvement. However, patients with isolated bone metastasis at presentation may have a longer survival. Therapeutic options for BC bone metastases often include systemic anticancer therapy (endocrine, chemotherapy, monoclonal antibodies, and/or other targeted therapies), which is largely dependent on the immunohistochemical (IHC) repertoire of the cancer for the prognostic markers [estrogen (ER) and progesterone receptors (PR), Ki-67, p53, and Her-2/neu] at its osseous metastatic site. Traditionally, specimens obtained from the bone metastasis require decalcification, which may affect the immunoreactivity of these prognostic markers. To the best of our knowledge, limited studies describe the effect of decalcification on immunoexpression of the above-mentioned markers. A detailed illustration of the effect of decalcification on BC specimens in a real-time manner is lacking in the literature. OBJECTIVE: Herein, we sought to determine the impact of decalcification on the IHC expression pattern of the above listed markers on BC tissue following decalcification. DESIGN: After Institutional Review Board approval, sections from the residual tumor specimens were collected prospectively from 15 BC excision specimens and 1 curetting from a BC bone metastasis. The sections (3 to 6 sections/case) for decalcification were collected following routine submission for pathologic evaluation. The sections were subjected to hydrochloric acid (HCl)-based Decal Stat decalcifying solution for 2, 12, 18, and 24 hours in each case. IHC studies for ER, PR, Ki-67, p53, and Her-2/neu were performed on 1 representative section of the regularly processed tumor block and 1 decalcified tumor block from each time point. Scoring of ER and PR were performed according to the Allred scoring system. Scoring of Her-2/neu was performed according to CAP/ASCO guidelines. RESULTS: The tumors comprised 11 grade 3 invasive ductal carcinomas, 2 grade 2 invasive ductal carcinomas, 2 grade 3 invasive lobular carcinoma, and 1 metastatic BC to bone. Nine cases showed Allred score 8 for ER, 1 case showed Allred score 4, 1 case showed Allred score 2, and the remaining 5 were ER negative. For PR, 1 showed Allred score 8, 2 Allred score 7, 4 Allred score 6, 1 each Allred score 5 and score 2 with the remainder negative for PR. Ki-67 ranged from 5% to 95%. Five cases showed p53 overexpression ranging from 35% to 95%. Five cases each showed 3+, 6 cases showed 2+ Her-2/neu, 3 cases showed 1+ Her-2/neu, and the remaining 2 were negative. All specimens demonstrated decline in ER, PR, Ki-67, and p53 immunoreactivity after 2 hours of decalcification, with additional decline up to 24 hours. The most significant declines in immunoreactivity occurred with Ki-67 and p53. Most of the Her-2/neu cases with an equivocal score declined to zero after 24 hours of decalcification. However, 3 out of 11 cases showing Her-2/neu overexpression remained at the baseline scoring even after extended (24 h) decalcification. CONCLUSIONS: Our results demonstrated that the decalcification process affects the immunoreactivity of the prognostic BC markers. There is progressive loss of reactivity at 2 hours and beyond for markers with lower degrees of expression. In addition, heterogeneity in marker distribution progressed from diffuse to more focal beyond 1 hour.

Application of the combined FibroMeter vibration-controlled transient elastography algorithm in Chinese patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: The FibroMeter vibration-controlled transient elastography (FM VCTE) is a new formula combining the serum test FM and liver stiffness measurement (LSM) by VCTE. We tested the accuracy and utility of FM VCTE for fibrosis staging in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Two hundred fifteen NAFLD patients with LSM, FM NAFLD, FM VCTE, and other serum tests (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, BARD score, NAFLD fibrosis score, and aspartate aminotransferase-to-alanine aminotransferase ratio) performed 1 day before liver biopsy were evaluated. RESULTS: Sixty-nine (32.1%) and 43 (20.0%) patients had F2-4 and F3-4, respectively. LSM had higher diagnostic accuracy (area under receiver-operating characteristics curves [AUROC] 0.851 for F2-4, 0.940 for F3-4; Obuchowski index 0.937 ± 0.007) than all evaluated serum tests, while FM NAFLD was the most accurate serum test (AUROC 0.775 and 0.774; Obuchowski index 0.891 ± 0.013). FM VCTE had similar accuracy to LSM (AUROC 0.855 and 0.901; Obuchowski index 0.927 ± 0.009). LSM had excellent negative predictive values of 92.4% and 99.2% to exclude F2-4 and F3-4, but the positive predictive values (PPV) were only 71.4% and 61.0%, respectively. In patients with high LSM, the use of FM VCTE improved the PPV from 71.4% to 84.4% for F2-4 and from 61.0% to 88.9% for F3-4. Liver biopsy could be spared in around 50-65% of patients. CONCLUSIONS: Liver stiffness measurement alone can confidently exclude significant and advanced fibrosis in NAFLD patients. Using FM VCTE in patients with high liver stiffness can increase the positive predictive value to rule in F2-4 and F3-4.

Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients.

Although nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity, around 10%-20% of nonobese Americans and Asians still develop NAFLD. Data on this special group are limited. We therefore studied the severity and clinical outcomes of nonobese NAFLD patients. Consecutive NAFLD patients who underwent liver biopsy were prospectively recruited. We used the NASH Clinical Research Network system to score the histology. The Asian body mass index cutoff of 25 kg/m2 was used to define nonobese NAFLD. Among 307 recruited NAFLD patients, 72 (23.5%) were nonobese. Compared to obese patients, nonobese patients had lower NAFLD activity score (3.3 ± 1.3 vs. 3.8 ± 1.2; P = 0.019), mainly contributed by steatosis (1.7 ± 0.8 vs. 2.0 ± 0.8; P = 0.014) and presence of hepatocyte ballooning (60.9% vs. 73.4%; P = 0.045). Similarly, nonobese patients had lower fibrosis stage (1.3 ± 1.5 vs. 1.7 ± 1.4; P = 0.004), serum cytokeratin-18 fragments (283 vs. 404 U/L; P < 0.001) and liver stiffness measurement by transient elastography (6.3 vs. 8.6 kilopascals; P < 0.001). By multivariate analysis in nonobese patients, only elevated serum triglyceride level was independently associated with higher NAFLD activity score (adjusted odds ratio [OR], 1.644; P = 0.021), whereas elevated creatinine level was the only factor associated with advanced fibrosis (adjusted OR, 1.044; P = 0.025). After a median follow-up of 49 months, 6 patients died, 2 developed hepatocellular carcinoma, and 1 had liver failure, all of whom were in the obese group. CONCLUSION: Nonobese NAFLD patients tend to have less-severe disease and may have a better prognosis than obese patients. Hypertriglyceridemia and higher creatinine are the key factors associated with advanced liver disease in nonobese patients. (Hepatology 2017;65:54-64).

Transaxillary thyroidectomies: a comparative learning experience of robotic vs endoscopic thyroidectomies.

OBJECTIVE: Robotic and endoscopic approaches have become more accepted in thyroid surgery, with current literature documenting the experience of high-volume centers. We adopted both approaches concurrently, and this series presents our initial experience to assess the more practical option for low- to moderate-volume centers starting out with transaxillary thyroidectomies. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Over a period of 4 years, 101 patients underwent transaxillary thyroidectomies, of whom 48 underwent robotic thyroidectomy and 53 underwent endoscopic thyroidectomy. Data analysis includes patient characteristics, procedure time, thyroid pathology, and postoperative complications. A survey was conducted among surgeons to assess the subjective experience. RESULTS: Endoscopic hemithyroidectomies had a significantly shorter duration of operation (145.8 minutes) vs that of robotic hemithyroidectomies (193.6 minutes), P < .001. The mean time taken for the first 5 hemithyroidectomies vs the last 5 hemithyroidectomies showed a greater drop in the endoscopic group (49.1%) vs the robotic group (18.6%). There were 2 cases of transient recurrent laryngeal nerve injury. In the surgeon survey, the endoscopic technique was perceived to have less need for peripheral support, while the robotic technique was preferred for its shorter learning curve. CONCLUSION: In terms of outcome, both techniques are comparable at least in the initial phase. Based on our early experience, the endoscopic technique may be less intuitive with a longer learning curve, although at steady state, it may be the quicker procedure. This is relevant for low- to moderate-volume centers starting their transaxillary thyroidectomy program.

Comparison of PAX6 and PAX8 as immunohistochemical markers for pancreatic neuroendocrine tumors.

To compare the utility of PAX6 and PAX8 as immunohistochemical markers for neuroendocrine tumors (NETs) of pancreatic origin, we performed PAX6 and PAX8 immunostains on 178 NETs, including 110 primary NETs (26 pancreatic, 10 gastric, 12 duodenal, 22 jejuno-ileal, 10 rectal, 30 pulmonary) and 68 NETs metastatic to the liver (24 pancreatic, 1 duodenal, 37 jejuno-ileal, 1 rectal, 5 pulmonary). Among primary NETs, PAX6 and PAX8 were positive in 65 % (17/26) and 73 % (19/26) of pancreatic, 0 % (0/10) and 10 % (1/10) of gastric, 92 % (11/12) and 92 % (11/12) of duodenal, 0 % (0/22) and 0 % (0/22) of jejuno-ileal, 90 % (9/10) and 80 % (8/10) of rectal, and 0 % (0/30) and 23 % (7/30) of pulmonary NETs, respectively. PAX6 and PAX8 positivity was seen in 46 % (11/24) and 50 % (12/24) of metastatic pancreatic NETs to the liver, respectively. None of the nonpancreatic NETs metastatic to the liver were immunoreactive for either PAX6 or PAX8. PAX6 showed a slightly but statistically significant higher specificity for pancreatic NETs than did PAX8 (P = 0.039), while the sensitivities were similar (P = 0.51). PAX6 had the additional advantages over PAX8 of not exhibiting nonspecific cytoplasmic staining of tumor cells and only infrequently staining background lymphocytes. Since rectal NETs rarely present with metastatic disease, positive staining of a metastatic NET of unknown primary origin for PAX6 and/or PAX8 favors a pancreatic or duodenal origin. This information may be helpful in directing further diagnostic studies to identify the primary site of the metastatic tumor.

Uroplakin II outperforms uroplakin III in diagnostically challenging settings.

AIMS: We performed a head-to-head comparison of an antibody against uroplakin III (UP3) and a new uroplakin II (UP2) antibody that remains untested in diagnostically challenging settings. METHODS AND RESULTS: We immunostained high-grade bladder neck carcinomas (n = 35), high-grade upper tract urothelial carcinomas (UC) and renal carcinomas (n = 85), metastases of UC (n = 30) and a multicancer tissue microarray (n = 88) for UP3 and UP2, and scored staining intensity and proportion. UP3 showed membranous plaque-like expression, while UP2 staining showed both membranous and cytoplasmic positivity. Significantly greater intensity (P = 0.003) and proportion (P = 0.03) of staining was noted for UP2 among bladder neck lesions, with UP2 staining showing greater sensitivity (63% versus 19%) and similar specificity (95% versus 100%) for UC over prostate carcinoma (P = 0.02). Among upper tract lesions, UP2 staining showed greater intensity and proportion than UP3 (both P < 0.001), including improved sensitivity (68% versus 23%) and equal specificity (both 100%) for UC (P = 0.006). Among UC metastases, UP2 staining showed greater intensity and proportion (both P < 0.001) with higher sensitivity (73% versus 37%, respectively, P = 0.001). Of 88 additional cases tested, no non-urothelial cases stained for either UP. CONCLUSIONS: The UP2 antibody outperforms the UP3 antibody, including in diagnostically challenging settings, and is a useful addition to the armamentarium of biomarkers for UC.

Clinicopathological significance of HER2/neu genetic heterogeneity in HER2/neu non-amplified invasive breast carcinomas and its concurrent axillary metastasis.

BACKGROUND: HER2/neu (HER2) is a significant prognostic marker for breast carcinomas. Recently, new guidelines defining HER2 genetic heterogeneity (GH) were published by the College of American Pathologists. AIMS: To determine the prevalence of HER2 GH as defined in primary invasive breast carcinoma, to determine its relationship with prognostic variables and to investigate its impact on concurrent axillary metastasis. METHODS: 235 consecutive infiltrating breast carcinomas were evaluated for GH (defined as presence of 5-50% of neoplastic cells with HER2/CEP17 ratio >2.2) using fluorescence in situ hybridisation. Pathological features of carcinomas with GH were compared with those lacking GH. GH was also evaluated in a subset of 37 paired primary carcinomas and its concurrent axillary nodal metastases using dual in situ hybridisation. RESULTS: HER2 GH was noted in 27% of HER2 negative breast carcinomas. These carcinomas demonstrated aggressive characteristics (larger size, higher grade and greater incidence of lymph node metastasis) in comparison with HER2 negative cases without GH. Higher levels of GH were associated with the equivocal HER2 status. GH was maintained in the concurrent lymph node metastases with some variations; however, two cases with clusters of HER2 amplified cells in the primary carcinoma showed HER2 amplification in the nodal metastasis. CONCLUSIONS: HER2 GH is present in 27% of breast carcinomas, portends an aggressive phenotype and contributes to the equivocal HER2 status. Evaluation of the HER2 status in nodal metastasis of select primary carcinomas with GH may be beneficial before treatment selection.

Evaluation of a triple combination of cytokeratin 20, p53 and CD44 for improving detection of urothelial carcinoma in urine cytology specimens.

BACKGROUND: Atypical urine cytology results trigger cystoscopy or molecular tests, both of which are costly, complex and difficult to perform tests. Several immunostains are being investigated to improve cancer detection; however, cytology material is limited and restricts the use of multiple immunostains. This study was designed to determine the utility of a cocktail of three stains, cytokeratin (CK20), p53 and CD44 in urine cytology samples for improving the detection of urothelial carcinoma. MATERIALS AND METHODS: Urine cytology specimens with cell blocks containing adequate cytologic material between 2005 and 2010 and subsequent follow-up biopsy and/or Urovysion test (102 cases including 29 negative, 56 atypical and 17 malignant) were included in the study and evaluated with the triple stain. Results were first validated on the positive and negative cases and then applied to the atypical cases to determine the utility in the diagnosis of urothelial carcinoma. RESULTS: Based on the validation and published literature, two distinct immunoprofiles were defined - malignant, characterized by at least five CK20 and/or p53 positive atypical cells and reactive, all other staining patterns. The malignant immunoprofile showed 88% sensitivity, 78% specificity, 74% positive predictive value (PPV) and 90% negative predictive value (NPV) for detecting urothelial carcinoma. These values improved to 95% sensitivity and 96% NPV when low-grade urothelial carcinoma cases were excluded. SUMMARY: Our results indicate that the triple stain is an inexpensive, easy to perform test most useful for differentiating high-grade urothelial carcinoma from its mimics. However Inclusion of CD44 in the cocktail did not provide additional value and is best excluded.

Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors.

Ki-67 proliferative index (Ki-67 index) is suggested to be an important prognostic variable and is included as one of the grading parameters for neuroendocrine tumors. The present study was undertaken to determine the usefulness of the Ki-67 index and the corresponding tumor grade in predicting progression-free survival (PFS) of patients with ileal well-differentiated neuroendocrine tumors (wNETs). Tumors from 57 patients with ileal wNETs were studied. Immunohistochemical staining for Ki-67 was performed on the primary as well as selected metastatic tumors and quantitated by computer-assisted image analysis using the Ariol system. The tumors were graded based on mitotic activity and Ki-67 index. Clinical and pathological variables affecting the PFS were analyzed. There were 29 women and 28 men, with a mean age of 59 years. At the time of initial presentation, 8 patients (14%) had localized disease (stages I and II), 29 patients (51%) had regional (nodal/mesenteric) spread (stage III), and 20 patients (35%) had distant metastasis (stage IV). Twelve patients experienced disease progression during subsequent follow-up. Patients with initial stage IV disease were more likely to experience disease progression (P = .005). Additionally, higher histological grade (as determined by Ki-67 index >2%) was associated with a decreased PFS (P = .001). Ki-67 index greater than 2% at either the primary site or the metastatic site was found to be the only significant predictor of PFS after consideration of all other variables in an adjusted analysis. In conclusion, the Ki-67 index predicts PFS of patients with ileal wNETs.

Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma.

HER2 overexpression and amplification have been studied as a therapeutic and prognostic target in a number of human cancers, including esophageal, gastric, and colorectal adenocarcinomas. However, HER2 status has not been well investigated in primary small intestinal adenocarcinoma, probably because of its rarity. In this study, we conducted immunohistochemical analysis and fluorescence in situ hybridization (FISH) for HER2 on 49 primary nonampullar small intestinal adenocarcinomas. The results showed a complete lack of HER2 protein expression in 47 cases (96%) by immunohistochemical analysis. Only 2 cases (4%) showed a 1+ staining pattern. No tumors exhibited 2+ or 3+ HER2 immunoreactivity. By FISH, none of the tumors, including those with 1+ HER2 immunoreactivity, exhibited HER2 gene amplification. These observations demonstrate that HER2 protein overexpression and gene amplification are infrequent events, if they occur at all, in small intestinal adenocarcinoma. Thus, routine immunohistochemical and/or FISH testing for HER2 for potential targeted anti-HER2 therapy may not be beneficial for patients with primary small intestinal adenocarcinoma.

Expression of hepatocyte antigen in small intestinal epithelium and adenocarcinoma.

Hepatocyte antigen is recognized by antibody Hep Par 1, a widely used diagnostic immunomarker for hepatocellular carcinoma and tumors with hepatoid differentiation. Hepatocyte antigen expression has also been detected in nonneoplastic small intestinal epithelium, but expression in small intestinal adenocarcinoma has not been well investigated. We immunohistochemically examined 39 nonampullary small intestinal adenocarcinomas for hepatocyte antigen expression; 34 cases contained normal-appearing nonneoplastic small intestinal mucosa on the same tissue sections. In 30 cases (88%), the nonneoplastic mucosa exhibited granular cytoplasmic Hep Par 1 staining exclusively in the epithelium. Only 9 small intestinal adenocarcinomas (23%) showed focal positive cytoplasmic staining. Nonneoplastic colonic epithelium was negative for Hep Par 1. In 31 colorectal adenocarcinomas, 3 (10%) showed positive staining for Hep Par 1 (1 diffuse, 2 focal), a frequency not different from that for small intestinal adenocarcinomas (P = .2467). Tumors expressing hepatocyte antigen did not exhibit evidence of hepatoid differentiation and were histologically indistinguishable from hepatocyte antigen-negative tumors. Hepatocyte antigen immunoreactivity is selectively expressed in nonneoplastic small intestinal enterocytes but not in colonocytes, suggesting a potential physiologic role in intestinal biology. Whether the loss of antigen expression in a large number of small intestinal adenocarcinomas serves a role in small intestinal tumorigenesis remains to be investigated.