Role of dual-point 18F-FDG-PET/CT in the diagnosis of pancreatic adenocarcinoma, in patients with and without concomitant chronic pancreatitis: Comparison with CECT and EUS.

PURPOSE: The aim of this study was to evaluate the diagnostic performance of dual-time-point-PET/CT, CECT and EUS + FNA in diagnosing pancreatic-ductal-adenocarcinomas (PDAC), in context of concomitant Chronic Pancreatitis (CP). METHODS: 18F-FDG-PET/CTs were prospectively acquired in 22 confirmed CP and 23 confirmed PDAC patients (calculated for 90% power); and cut-offs of 2.2 for early-SUV(∼1hr), 2.4 for delayed-SUV(∼3hr) and 1.36 for Retention-index (RI), were derived. These cut-offs were validated in PET/CTs of 75 patients (51.9 ± 13.3years; 54 men) with pancreatic masses of unknown nature. Comparisons were made with triple-phase-CECT (73 patients) and EUS + FNA (54 patients). Histopathology was obtained in 68 patients (including all PDACs) and 7 were followed up for minimum of 2 years. RESULTS: In patients without concomitant CP, sensitivity, specificity and accuracy for diagnosing malignancy in standard-acquisition-PET/CT, dual-time-point-PET/CT, CECT and EUS + FNA were 97.4%, 83.3%, 94.0%; 97.4%, 75.0%, 92%; 94.6%, 66.7%, 87.8% and 92.6%, 88.9%, 91.7% respectively. Corresponding values in patients with concomitant CP were 88.9%, 57.1%, 80.0%; 100%, 57.1%, 88%; 82.4%, 57.1%, 75% and 100%, 100%, 100% respectively. In lesions ≤2 cm (AJCC-T1), dual-time-point-PET/CT was the most sensitive (95.8%). ROC-analysis revealed significantly higher area-under-the-curve for RI over early-SUV (p = 0.002) in cases with concomitant CP only. In patients with confirmed liver-metastases, PET/CT and CECT identified 15/16 and 13/16 lesions. PET/CT identified additional lung-metastases in 3 and bone-metastasis in one patient. CONCLUSION: In patients without concomitant CP and with larger lesions, PET/CT and CECT are equivocal as screening modalities, with no benefit of dual-time-point-PET/CT acquisitions. However, in patients with concomitant CP and smaller lesions, dual-time-point PET/CT is better; with sensitivity comparable to EUS + FNA.

Pathology of celiac disease: a brief review.

Celiac disease is a gluten or prolamine-induced immunological disorder primarily affecting the intestines. Celiac disease is often missed since not only are clinical findings 'not typical' but also because many cases are asymptomatic. The diagnosis is based on a constellation of clinical, serological and histological findings in a duodenal biopsy, in addition to HLA genotype.and response to a gluten-free diet.Although some guidelines suggest that histology may not mandatory in every case, by and large changes in mucosal biopsies of the duodenum still remain an important diagnostic tool. The evaluation of a duodenal biopsy requires a properly oriented and satisfactory hematoxylin & eosin stained paraffin section. A poorly oriented and technically suboptimal biopsy is not uncommonly the reason for erroneous interpretation. An increase in intraepithelial lymphocytes [IELs] and an alteration of the crypt: villus ratio forms the basis of diagnosis. These are semiquantitavely classified. Despite varying opinions related to the cut-off values of IELs and findings that recommend appropriate site, number and size of the biopsy specimens, the sensitivity of biopsies vary from 90%-100%. Interpretation of histological findings require correlation with other evidences since the changes in duodenal biopsy may be similar to those seen in a host of other diseases including tropical sprue. It must also be mentioned that in the Indian subcontinent is that reference values for normal duodenal biopsies are lacking, making interpretation difficult especially when changes are mild. Histological changes in the duodenal mucosa often take months to normalize after clinical remission. This is a review of various aspects related to the histological changes in duodenal mucosal biopsies that aid in the diagnosis and follow-up of cases of celiac disease.

Helicobacter pylori in gallbladder mucosa in patients with gallbladder disease.

BACKGROUND: Helicobacter species have been found to be associated with biliary tract diseases. This prospective study was done to determine the prevalence of H. pylori in the biliary tract of patients suffering from gallbladder disease. METHODS: Forty-nine patients undergoing laparoscopic/open cholecystectomy for benign biliary tract diseases were investigated with urea breath test for H. pylori infection of gastric antrum. Bile and gallbladder tissues were studied for presence of H. pylori by rapid urease test, histopathological examination, culture and PCR analysis. Gallbladder specimens from two patients who underwent Whipple's operation and from 10 cadavers were studied as controls. RESULTS: The mean (SD) age of patients was 42.4 (11.1) years. Urea breath test was positive in 17 (34.6%) cases. Rapid urease test was negative in all the cases. There was no evidence of H. pylori infection of gallbladder on histopathological examination using H&E, Giemsa and Warthin Starry stains. H. pylori DNA were detected in 16 patients (32.6%) and none of the 12 controls by PCR analysis (p = 0.025). The presence of H. pylori DNA in bile and/or gallbladder was associated with positive urea breath test, (p < 0.0001). Other factors like age, gender, jaundice and cholestasis were not associated with H. pylori infection of bile and gallbladder. CONCLUSIONS: Nearly three quarters of patients with positive urea breath test have detectable H. pylori DNA in gallbladder tissue. The significance of these findings needs to be further evaluated.

Bone marrow mononuclear stem cell infusion improves biochemical parameters and scintigraphy in infants with biliary atresia.

PURPOSE: To evaluate early postoperative results in a case controlled study following clinical use of stem cells in extrahepatic biliary atresia (EHBA). METHODS: From July 2005 to March 2008, 30 cases of suspected EHBA were divided in two groups in an intervention study. Group A received autologous mononuclear bone marrow stem cells at the time of Kasai or after Kasai. In Group B, only Kasai was performed. Liver function tests on postoperative day 7 were compared. Serum bilirubin, clinical status, hepatic scintigraphy and survival at 6 months and 1 year were compared. RESULTS: Mean age was 136 (74-275) days in Group A and 99.7 (56-172) days in Group B. Preoperative values of serum bilirubin (SB), aspartate aminotransferase (AST), alanine aminotransferase and alkaline phosphatase (ALP) were comparable between the groups though there was significant difference in postoperative SB, AST and ALP (p = 0.014, 0.0041, 0.0005), with and without the use of stem cells. The median post stem cell SB was 6.9 (0.5-11.6) mg/dl in Group A versus 10.1 (5.6-26.3) mg/dl in Group B. Median SB at 6 months follow-up was 0.6 (0.5-5.4) mg/dl in Group A versus 7.6 (0.8-9.2) mg/dl in Group B (p = 0.028). There was a significant difference in episodes of cholangitis at 6 months postoperatively between the two groups (p = 0.024). Hepatic scans done at <3 months; >3 months follow-up showed prompt excretion in 80% (4/5); 85.7% (6/7) in Group A versus 20% (1/5); 50% (1/2) in Group B. Survival at 6; 12 months' follow-up was 45.5%; 27.3% in Group A versus 33.3%; 6.7% in Group B. Median postoperative survival was 181 (139,223) days in Group A versus 123 (65,181) days in Group B. CONCLUSION: Significant biochemical and scintigraphic improvement was noted following stem cell therapy in biliary atresia, probably attributable to anti-inflammatory action of stem cells.

Apoptotic protein expression in favorable-histology Wilms tumor correlates with tumor recurrence.

PURPOSE: Outcome for patients with Wilms tumor (WT) with favorable histology is good. Deletions of chromosomes 1p and 16q impart a poorer outcome. Value of apoptotic protein expression is not clear. METHODS: Expression of four immunohistochemically detectable apoptosis-regulating proteins (bcl-2, bcl-x, bax and p53) were analyzed in 30 specimens of WT and compared to recurrence and recurrence-free survival (RFS). RESULTS: The 30 patients included ranged from 4 to 72 months in age (mean 31). The mean available follow-up was 35.3 months (range 1-54). Six patients developed recurrence. The 5-year RFS for blastema-predominant tumors was 40% as compared to 91% for triphasic histology which was significant (p = 0.048). The 5-year RFS in patients with bcl-2 negative tumors was 63% as compared to 100% for bcl-2 positive tumors, the difference being significant (p = 0.019). The 5-year RFS in patients with p-53 positive tumors was 27% as compared to 91% for p-53 negative tumors; however, this difference in the RFS was not statistically significant (p = 0.143). bax and bcl-x expression were not related to the RFS. CONCLUSIONS: Tumors that are bcl-2 negative have a relatively higher recurrence rate and a poorer RFS. They may benefit from a more intensive follow-up regime for early detection of recurrence.

Primary pulmonary lymphoma presenting as lung mass.

The commonest cause of lung mass in an elderly patient is bronchogenic carcinoma. We are reporting an unusual case of lung mass that was diagnosed following exploratory thoracotomy and pneumonectomy. Sputum examination, bronchoscopy and percutaneous fine needle aspiration cytology were inconclusive. On histopathology, a diagnosis of non-Hodgkin's lymphoma (NHL) was made. There was no involvement of any other site on detailed work up. The patient was advised chemotherapy.

Mesonephroid adenocarcinoma of the bladder and urethra: a case report.

Mesonephric or mesonephroid adenocarcinoma of the bladder may be a malignant form of nephrogenic adenoma or nephroid metaplasia. The lesion is rare, and to the best of our knowledge only 9 cases have been reported in the world literature. We report another case of mesonephroid adenocarcinoma of the bladder and urethra which was treated with transurethral resection and subsequent chemotherapy.

Differential activity of cathepsin L in human placenta at two different stages of gestation.

The implantation of blastocyst depends on the invasiveness of the syncytiotrophoblast, which penetrates the maternal decidua to establish the placenta. Cathepsin L, a lysosomal cysteine protease over-expressed in a variety of human malignancies, has been implicated in tumour invasion and metastasis. Specific inhibitors of cathepsin L inhibit the invasion of amnion by murine tumour cells. Previous studies have revealed that tumour and trophoblast invasiveness are mediated by shared factors, like metalloproteinases and laminin. Several proteases closely related to cathepsin L have recently been reported in the placentae of different species. In the present study, we demonstrate the expression of cathepsin L in human placenta by immunohistochemical analysis and RT-PCR followed by Southern hybridization. The activity of cathepsin L against the synthetic dipeptidyl substrate, Cbz-Phe-Arg-N-Methylcoumarin, was assayed. E-64, a specific inhibitor of cathepsin L was used to confirm that the enzyme activity being measured was due to cathepsin L. We observed the specific activity of cathepsin L in first trimester placenta to be significantly higher as compared to the term placenta. However, the levels of placental cathepsin L mRNA were comparable at these two stages of gestation. The increased enzymatic activity of cathepsin L in the invasive phase of placentation taken together with its previously established role in tumour invasion and metastasis indicates the involvement of this protease in trophoblast invasion.

Experimental unilateral undescended testis: gubernaculectomy and anchoring or direct suture fixation?

This study was designed to evaluate whether creation of a unilateral undescended testis (U/L UDT) in rats by direct fixation of the testis can lead to changes in the contralateral (C/L) descended testis, and if so, whether this inherent problem of the model could be eliminated by anchoring the divided gubernaculum to indirectly fix the testis. Thirty male newborn rats were divided into three groups of 10 each and the procedure done on the 2nd day of life to create U/L UDT according to the group allocated: group I: sham-operated; group II: anchoring the gubernaculum after gubernaculectomy; group III: Direct suture fixation of the testis. Fertility, C/L testicular weight (TW), Johnsen score, seminiferous tubular diameter (STD), DNA flow cytometry, and serum anti-sperm antibodies (ASA) were studied. Fertility, C/L TW, Johnsen score, STD, and haploid cell population were significantly reduced in group III compared to group II, while significantly higher titers of ASA were found in group III. Gubernaculectomy and anchoring the gubernaculum to the anterior abdominal wall is a better technique of creation of experimental UDT, as direct fixation of the testis is potentially detrimental to the C/L normal, descended testis.

Effect of cyclosporine on fertility in male rats.

The effect of cyclosporine (CsA) on fertility has assumed greater importance with the increasing numbers of pediatric transplantations being performed all over the world. Conflicting reports on the effects of CsA on sex hormones are available. This experimental animal study was designed to examine the effect of CsA on testicular weight, sperm counts, seminiferous tubular diameter (STD), testicular morphology, DNA flowcytometry, sex hormone levels, and fertility in male rats. Those rats who received CsA (20 mg/kg per day) showed significant reductions in testicular weight (P < 0.05), sperm count (P < 0.01), Johnsen score (P < 0.05), STD (P < 0.01), serum testosterone levels (P < 0.05), haploid cell population (P < 0. 001) in the testis, and fertility (P < 0.001) compared to those receiving CsA 10 mg/kg per day and control rats. These findings will have an important bearing for children receiving cyclosporine for long periods to guide the physician in optimally adjusting long-term treatment.

Fertility and unilateral undescended testis in the rat model II.

Continuing experimental work on the effect of experimentally created unilateral undescended testis (UL-UDT) in neonatal rats, this study examined the fertility and correlated it to contralateral (CL) testicular morphology, seminiferous tubular diameter (STD), DNA flowcytometry, and the presence of serum anti-sperm antibodies (ASA) at 120-135 days of age. In our previous reported work, the fertility of rats with UL-UDT at 65-80 days of age was the same as that of controls. In the present study the rats with UL-UDT had significantly reduced fertility (P < 0.01) compared to controls, even though the Johnsen scores and mean STD of the CL testicular tissue were comparable. DNA flowcytometry demonstrated a significant decrease (P < 0.001) in haploid cell population in the CL testicular tissue of rats with UL-UDT. Furthermore, the rats with UL-UDT who either received an immunosuppressive or in whom the UDT was excised early showed almost normal fertility and DNA histograms like those of controls. Significantly high titres of serum ASA were detected only in the group with UL-UDT when tested at 135 days of age. From these results, in combination with earlier results on similar work, it may be inferred that UL-UDT causes immunologically-mediated, progressive damage to the CL descended testis, leading to a decrease in fertility in rats.

Grading of cellular rejection after orthotopic liver transplantation.

All 684 post-orthotopic liver transplantation (OLT) liver biopsies performed at the Royal Free Hospital (RFH) between 1988 and 1993, from 120 patients, were reviewed in order to try to define the relative importance of the histological features of immunosuppression-responsive cellular rejection. Twenty histological features considered to be possible contributors to the diagnosis of cellular rejection were documented in a binary (present/absent) fashion. These features in 106 biopsy specimens obtained 1 to 8 days after OLT were analyzed using stepwise logistic discriminant analysis. All clinical and treatment records were reviewed, and each biopsy specimen was assigned to a diagnostic category depending on these records and follow-up information. Important determinants of the histological diagnosis of cellular rejection (which occurred in 84 of the 106 cases) were moderate/severe mixed portal inflammation, eosinophils, endotheliitis, and bile duct damage. When these all occurred together, the odds of rejection increased 3.6-fold. The original histological diagnosis was recorded, and each biopsy specimen showing cellular rejection was regarded according to the specific criteria of Snover et al., Demetris et al., and a novel RFH scoring system. The latter consists of evaluating portal inflammation, endotheliitis, eosinophils, and bile duct damage, each on a 0 to 3 scale (none, mild, moderate, or severe, respectively) and summation. The resulting cellular rejection score thus can range from 0 to 12. The agreement between the different scoring systems was analyzed using K statistics, and there was good concordance (K, 0.64 to 0.78), despite different histological criteria being used to derive each score. Each system showed a similar degree of sensitivity (87% to 96%). The specificity ranged from 59% to 77%. We conclude that the histological diagnosis of cellular rejection relies mainly on the previously described features of mixed portal inflammation, endotheliitis, eosinophils, and duct damage. There is scope for unification and simplification of the existing grading systems, which depend on differing criteria, and we suggest one such scheme.

Treatment of recurrent desmoid tumour with tamoxifen.

A 30 year old woman with aggressive fibromatosis (desmoid) of the left upper arm and scapular region was treated with wide excision. Two years later she presented with extensive local recurrence of the scapular and deltoid regions. She was treated with tamoxifen (20 mg daily) and, over the next 6 months, the tumour regressed. She has been recurrence-free for the past year. We suggest that, in patients with desmoid tumours, hormone receptor determination and hormone therapy be attempted before subjecting patients to any form of radical treatment with surgery, radiotherapy or chemotherapy.