Multiagent neoadjuvant chemotherapy and tumor response are associated with improved survival in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NT) for borderline resectable pancreatic cancer (BRPC) has evolved to include multi-agent regimens and chemoradiation. We report our experience and compare outcomes of initially resectable pancreatic cancer (IRPC) vs BRPC receiving NT across two eras of chemotherapy regimens. METHODS: Data were collected retrospectively on pancreaticoduodenectomy patients between January 2008 and October 2015. Outcomes and survival were compared based on patient, laboratory and treatment factors. RESULTS: 195 patients were included and 133 had IRPC and 62 BRPC. IRPC operations were shorter (449 min vs 520 min, p = 0.003), had less blood loss (663 ml vs 954 ml, p = 0.002) and involved fewer vascular resections (29% vs 76%, p = 0.002). The rate of R0 resection was identical (82%, p = 1) and the IRPC group had higher node-positive ratio (19.3% vs 7.2% p < 0.0001). 15 patients received a single agent regimen while 47 received multi-agent regimens with 90% receiving radiation.Survival was similar between BRPC and IRPC (log-rank p = 0.7). Histopathologic response (CAP grade 0 or 1) was not associated with survival (p = 0.13), but completion of ≥4 cycles of multi-agent pre-operative chemotherapy (p = 0.001) and complete response to NT (p = 0.04) were significant predictors of survival. CONCLUSIONS: BRPC patients treated with NT have similar morbidity and survival to their IRPC counterparts. Pathologic response and modern NT are associated with improved survival.

Molecular and histopathologic characteristics of multifocal papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is frequently multifocal, which can represent either intraglandular spread from a single primary tumor or multiple synchronous primary tumors (MSPTs). To distinguish and characterize these entities, we investigated whether multifocal PTCs contain genetically similar or different mutations and have particular histopathologic characteristics. In 60 cases of PTC with 2 to 4 discrete tumor foci, each focus was tested for BRAF, NRAS, HRAS, and KRAS point mutations and RET/PTC1 and RET/PTC3 rearrangements and analyzed for various histopathologic features. Overall, BRAF mutations were found in 43% of tumors, RAS in 27%, and RET/PTC in 2%. Four different patterns of mutation occurrence were identified: (i) 2 foci containing different mutations (30%); (ii) 1 tumor containing a mutation and another carrying no mutations (32%); (iii) both/all tumors containing the same mutation (25%); (iv) all tumors having no mutations (13%). The 30% of cases with 2 different mutations represent a group of tumors that are unequivocally MSPT. These tumors more commonly occurred in different lobes, although they could be located as close as 0.6 cm from each other. Moreover, MSPTs typically demonstrated distinct histologic variants/microscopic features, were encapsulated or had a smooth border, and showed no microscopic peritumoral dissemination. In conclusion, we demonstrate that at least 30% of multifocal PTCs represent unequivocal MSPTs that develop through distinct molecular alterations and that as many as 60% of multifocal PTCs are likely MSPTs. Histopathologically, MSPTs are typically located in different lobes, have distinct growth patterns, and do not show microscopic peritumoral dissemination.

Correlation of histopathologic/cytologic follow-up findings with vaginal ASC-US and ASC-H Papanicolaou test and HPV test results.

Current American Society of Colposcopy and Cervical Pathology recommendations about human papillomavirus (HPV) triage and further management for atypical squamous cells are pertinent to cervical Papanicolaou (Pap) tests. There are limited data on HPV detection in vaginal liquid-based cytology (LBC) specimens. The aims of this study were to determine whether adjunctive high-risk (HR)-HPV testing is useful for disease risk assessment in women with vaginal atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude HSIL (ASC-H) Pap results. We identified 1,125 ASC-US and 36 ASC-H vaginal Pap results with HR-HPV testing. Of the cases, 244 (21.7%) ASC-US and 21 (58%) ASC-H were HR-HPV+. Among ASC-US HR-HPV+ cases, 47.8% had a squamous intraepithelial lesion (SIL) compared with 4.7% of HR-HPV- cases. Among ASC-H HR-HPV+ cases, 75% (12/16) had SIL compared with 31% (4/13) in HR-HPV- cases. Our results indicate that HPV triage testing is a reasonable and cost-effective approach for women with ASC-US vaginal Pap results and also a useful option for women with ASC-H vaginal Pap results.

Correlation of histopathologic follow-up findings with vaginal human papillomavirus and low-grade squamous intraepithelial lesion Papanicolaou test results.

CONTEXT: Data on high-risk human papillomavirus (hrHPV) DNA test results in vaginal, liquid-based cytology (LBC) specimens and corresponding cytologic and histopathologic correlation data are limited. OBJECTIVE: To analyze follow-up correlation data associated with vaginal (after hysterectomy) low-grade squamous intraepithelial lesion (LSIL) LBC and hrHPV test results. DESIGN: Hospital records were searched for vaginal LSIL LBC and hrHPV results between July 1, 2005, and July 30, 2009. Histopathologic and Papanicolaou test follow-up correlation data were analyzed. RESULTS: During the study period, 2892 patients with test results from both posthysterectomy vaginal LBC and hrHPV were identified: 148 (5.1%) of the patients had vaginal Papanicolaou test results reported as LSIL, with hrHPV detected in 113 of the 148 patients (76.4%). Of 148 patients, 59 of those with vaginal LSIL including 48 (81.4%) with positive HPV testing and 11 (18.6%) with negative HPV testing results had a follow-up vaginal biopsy. Histopathologic vaginal intraepithelial neoplasia (VAIN) 2/3 was diagnosed in 7 of 59 patients (11.9%) with biopsies. In all 7 patients who were diagnosed with VAIN 2/3, hrHPV was detected in the LBC vial. No VAIN 2/3 diagnoses were documented in the biopsy specimens from the 11 patients with hrHPV(-) LSIL Papanicolaou test results. Histopathologic VAIN 2/3 was diagnosed from vaginal biopsies in 7 of the 48 patients (14.6%) with vaginal hrHPV(+) LSIL test results. CONCLUSIONS: Sensitivity and specificity of hrHPV test results associated with histopathologic follow-up diagnoses of VAIN 2/3 in patients with vaginal LSIL results were 100% and 21.2%, respectively. The positive predictive value of a vaginal hrHPV(+) LSIL result for a subsequent histopathologic VAIN 2/3 diagnosis was 14.6%. No cases of VAIN 2/3 were diagnosed in the 11 patients with vaginal hrHPV(-) LSIL results. Correlations of vaginal cytologic, histopathologic, and human papillomavirus findings were quite similar to correlation findings previously reported in older women with cervical LSIL test results.

Subperitoneal adenomucinosis following proctocolectomy for ulcerative colitis.

Adenomucinosis is a rare condition characterized by accumulation of large volumes of mucin, typically related to mucinous neoplasms of the appendix within the peritoneal space. Extraperitoneal adenomucinosis is an uncommon variant where mucin accumulates outside the peritoneal space and usually arises following surgery for mucinous appendiceal neoplasms. This is a case of subperitoneal adenomucinosis resulting from retention of a small fragment of rectal mucosa following proctocolectomy for ulcerative colitis 16 years prior. The patient presented with a slow-growing boggy perineal mass. Contrast-enhanced magnetic resonance imaging (MRI) showed the mass to be localized to the pelvis, without solid enhancing components, and correctly facilitated local surgical excision without the risk of peritoneal dissemination and accurately predicted benignity.

The diagnostic utility of p16 FISH and GLUT-1 immunohistochemical analysis in mesothelial proliferations.

Two promising ancillary tests used in the diagnosis of mesothelioma include GLUT-1 immunohistochemical analysis and fluorescence in situ hybridization (FISH) testing for the p16 deletion. This study compared the diagnostic usefulness of p16 FISH and GLUT-1 immunohistochemical analysis in the diagnosis of mesothelial proliferations in 158 cases with a diagnosis of benign (45.4%), atypical (10.4%), or malignant/mesothelioma (44.2%). Of the 70 benign cases, none had a deletion of p16 and 5 cases (7%) were positive for GLUT-1. Of the 68 mesotheliomas, 40 (59%) had a deletion of p16 (sensitivity, 59%; specificity, 100%) and 27 (40%) were positive for GLUT-1 (sensitivity, 40%; specificity, 93%). GLUT-1 showed lower sensitivity in pleural (56% vs 70%) and peritoneal (29% vs 51%) mesotheliomas (P = .004). Our results demonstrate that p16 FISH is a more sensitive and specific test than GLUT-1 immunohistochemical analysis and can be a more reliable ancillary tool to support the diagnosis of mesothelioma.

Prevalence of high-risk human papillomavirus in women with abnormal and normal vaginal ThinPrep Papanicolaou cytology.

OBJECTIVE: The significance of high-risk HPV (hrHPV) testing in the management of women with abnormal cervical Pap tests is well known. However, the data about the hrHPV detection and its significance in abnormal vaginal specimens are very limited. The purpose of this study was to assess the prevalence of hrHPV in women with abnormal vaginal smears. METHODS: Our Copath database system was searched to retrieve all the vaginal Pap tests with adjunctive HC2 hrHPV DNA test performed between July 1, 2005, and July 30, 2009. The results of hrHPV were reviewed in different TBS 2001 categories, in different age groups, and in white and African American women. RESULTS: During the study period, there were 1,320 vaginal ThinPrep Pap tests with adjunctive HC2 hrHPV, reported as atypical squamous cells of undetermined significance (n = 1,125), atypical squamous cells cannot rule out high grade (n = 36), low-grade squamous intraepithelial lesion (n = 148), and high-grade squamous intraepithelial lesion (n = 11). A positive hrHPV DNA result was obtained in a total of 387 cases (29.3%), which included 244 atypical squamous cells of undetermined significance (21.7%), 21 atypical squamous cells cannot rule out high-grade (58.3%), 113 low-grade squamous intraepithelial lesion (76.4%), and 9 high-grade squamous intraepithelial lesions (81.8%). Mean age was 56.5 years (range = 17-93 y). High-risk HPV-positive rate was 34.5% versus 24.9% in women aged 54 years or younger compared with those aged ≥ 55 years or older (p < .001) and 45.1% versus 27.3% in African American women compared with white women (p < .001). High-risk HPV DNA-positive rate was 2.6% among the 1,572 women with negative vaginal Pap tests. CONCLUSIONS: Our results show that prevalence of hrHPV in abnormal vaginal smears parallels that of cervical smears with equivalent degree of abnormality. The suggestion of reflex hrHPV testing as a tool in formulating the management plan for women with abnormal vaginal smears needs further attention.

High-risk HPV DNA detected in less than 2% of over 25,000 cytology negative imaged liquid-based Pap test samples from women 30 and older.

OBJECTIVE: The purpose of this study was to document the prevalence of high-risk HPV DNA (HPV) in the largest cohort of woman studied to date with negative ThinPrep Imaging system (TIS)-imaged Pap tests. METHODS: Women with negative (TIS)-imaged ThinPrep Pap Tests (TPPT) who also were tested for HPV were identified between July 1, 2005 and December 31, 2007 from a large women's hospital practice. HPV detection rates were compared for women with either presence or absence of a transformation zone/endocervical cell sample (EC/TZS). RESULTS: 26,558 negative TPPT also underwent HPV testing. HPV detection was higher in women younger than 30 and sharply declined in women 30-39 (P<0.001). Declining HPV detection rates continued in the 40-49 age group (age 30-39 vs. 40-49; 2.8% vs. 1.7%, P<0.001) and then levelled off. No statistically significant difference for HPV prevalence was identified comparing women with and without a TZ/ECS. CONCLUSION: This is the largest study to date documenting very low HPV detection rates in women screened cytology negative with computer-imaged liquid-based Pap methods now representing a major portion of the U.S. cervical cytology market. Findings of very low rates of HPV detection in 490 (1.9%) of 25,259 cytology negative women 30 and older extend and confirm previously reported findings in smaller study populations. Because HPV testing provides an objective measure of relative residual risk for cervical neoplasia after screening, these data are relevant to discussions on how best to combine cytology and HPV testing in screening low risk populations.

Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats.

Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague-Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-beta), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I-V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-beta, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds.

Bone marrow-derived mesenchymal stromal cells accelerate wound healing in the rat.

Bone marrow-derived mesenchymal stromal cells (BMSCs) are multipotential stem cells capable of differentiation into numerous cell types, including fibroblasts, cartilage, bone, muscle, and brain cells. BMSCs also secrete a large number of growth factors and cytokines that are critical to the repair of injured tissues. Because of the extraordinary plasticity and the ability of syngeneic or allogeneic BMSCs to secrete tissue-repair factors, we investigated the therapeutic efficacy of BMSCs for healing of fascial and cutaneous incisional wounds in Sprague-Dawley rats. Systemic administration of syngeneic BMSCs (2 x 10(6)) once daily for 4 days or a single treatment with 5 x 10(6) BMSCs 24 hours after wounding significantly increased the wound bursting strength of fascial and cutaneous wounds on days 7 and 14 postwounding. Wound healing was also significantly improved following injection of BMSCs locally at the wound site. Furthermore, allogeneic BMSCs were as efficient as syngeneic BMSCs in promoting wound healing. Administration of BMSCs labeled with iron oxides/1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate fluorescent dye revealed that systemically administered BMSCs engraft to the wound. The increase in the tensile strength of wounds treated with BMSCs was associated with increased production of collagen in the wound. In addition, BMSC treatment caused more rapid histologic maturation of wounds compared with untreated wounds. These data suggest that cell therapy with BMSCs has the potential to augment healing of surgical and cutaneous wounds.

Postmortem pathology of opportunistic infection in a HIV positive patient--a case report.

An autopsy case of HIV positive patient with multiple opportunistic infections is described. We received heart, lungs, spleen and both the kidneys along with pieces of cerebrum for anatomy and histopathological examination. Histology of organs revealed disseminated non-granulomatous necrotizing type of tissue reaction with superadded infection with Cryptococcus neoformans (C. neoformans) in liver and brain. Pneumocysts carini (P. carini) induced pneumonia in lungs, disseminated mycobacterial infection in spleen, lungs, liver and kidneys and acute fibrinous meningitis with superadded infection with C. neoformans in brain. Special stains were carried out to demonstrate different organisms.