An Ingested Bone Perforating Through the Stomach into the Superior Mesenteric Vein.

Here, we describe a case of an 86-year-old man presenting with several days of abdominal pain. Computed tomography (CT) demonstrated a radiopaque object penetrating through the stomach into the superior mesenteric vein. He was taken for exploratory laparotomy where a sharp object was noted to be extending through the posterior wall of the stomach. To control the body, an anterior gastrotomy was performed. There was no hemorrhage noted from the retroperitoneum. On gross inspection, the foreign body appeared to be consistent with a large fragment of bone. On discussion with the patient, he noted consuming a large pork chop prior to the onset of his abdominal pain. He recovered well without significant complication and was able to return home. Subsequent follow up confirmed his continued convalescence.

Improved outcomes for borderline resectable adenocarcinoma of the pancreas after neoadjuvant chemotherapy in a community cancer center.

BACKGROUND: Borderline resectable adenocarcinoma of the pancreas involves the major vascular structures adjacent to the pancreas and has traditionally led to poor resection rates and survival. Newer chemotherapy regimens have demonstrated improved response and resection rates. We performed a retrospective review of borderline resectable pancreatic cancers who presented to a community cancer program to determine the effect of neoadjuvant chemotherapy to improve resection rates and overall survival. METHODS: Records of all patients diagnosed with adenocarcinoma of the pancreas from January 1, 2015 to December 31, 2019 were reviewed to determine stage at presentation, resectablility status, treatment methods, surgical resection and survival. Borderline resectable status was determined by preoperative imaging in agreement with published criteria from the National Comprehensive Cancer Network (NCCN) Guidelines 2.2021. Data was collected and analyzed by standard t-test. This study was approved by the institution's IRB. RESULTS: During this time period 322 patients were diagnosed with ductal adenocarcinoma of the pancreas of which 151 (47%) were unresectable, 31 (10%) were locally advanced, 70 (22%) were borderline resectable, and 69 (21%) were resectable at the time of presentation. 36 (51%) of the borderline resectable patients underwent neoadjuvant chemotherapy at our institution with either FOLFIRINOX or gemcitibine/nab-Paclitaxel regimens and served as the basis for this analysis. After neoadjuvant chemotherapy 24 (68%) of the borderline-resectable patients were deemed suitable for surgical exploration. At exploration, 15 (64%) were resected with 9 (60%) achieving margin-free resection on final pathology. The overall survival of those that underwent resection was increased by 19.6 months compared to those that did not undergo surgery (35.4 versus 15.8 mos, p < 0.01). Overall morbidity after resection was 46% (33% class 1 or 2, 13% class 3) with 0% mortality at 90 days. CONCLUSIONS: Use of neoadjuvant chemotherapy for borderline resectable adenocarcinoma of the pancreas results in improved resection rates and overall survival in resected patients. This management strategy for ductal adenocarcinoma of the pancreas is safe and feasible in a community-based cancer program.

Targeted polymeric nanoparticles for drug delivery to hypoxic, triple-negative breast tumors.

High recurrence and metastasis to vital organs are the major characteristics of triple-negative breast cancer (TNBC). Low vascular oxygen tension promotes resistance to chemo- and radiation therapy. Neuropilin-1 (NRP-1) receptor is highly expressed on TNBC cells. The tumor-penetrating iRGD peptide interacts with the NRP-1 receptor, triggers endocytosis and transcytosis, and facilitates penetration. Herein, we synthesized a hypoxia-responsive diblock PLA-diazobenzene-PEG copolymer and prepared self-assembled hypoxia-responsive polymersomes (Ps) in an aqueous buffer. The iRGD peptide was incorporated into the polymersome structure to make hypoxia-responsive iRGD-conjugated polymersomes (iPs). Doxorubicin (DOX) was encapsulated in the polymersomes to prepare both targeted and non-targeted hypoxia-responsive polymersomes (DOX-iPs and DOX-Ps, respectively). The polymeric nanoparticles released less than 30% of their encapsulated DOX within 12 hours under normoxic conditions (21% oxygen), whereas under hypoxia (2% Oxygen), doxorubicin release remarkably increased to over 95%. The targeted polymersomes significantly decreased TNBC cells' viability in monolayer and spheroid cultures under hypoxia compared to normoxia. Animal studies displayed that targeted polymersomes significantly diminished tumor growth in xenograft nude mice. Overall, the targeted polymersomes exhibited potent anti-tumor activity in monolayer, spheroid, and animal models of TNBC. With further developments, the targeted nanocarriers discussed here might have the translational potential as drug carriers for the treatment of TNBC.

Implementation of a standardized approach to borderline resectable pancreatic cancer in a multisite community oncology program.

BACKGROUND: Treatment paradigms for borderline resectable pancreatic cancer are evolving with increasing use of neoadjuvant chemotherapy and neoadjuvant chemoradiation. Variations in the definition of borderline resectable pancreatic cancer and neoadjuvant approaches have made standardizing care for borderline resectable pancreatic cancer difficult. We report an effort to standardize management of borderline resectable pancreatic cancer throughout Sanford Health, a large community oncology network. METHODS: Starting in October 2013, cases of pancreatic adenocarcinoma without known metastatic disease were categorized as borderline resectable pancreatic cancer if they met ≥ 1 of the following criteria: (1) abutment of superior mesenteric, common hepatic, or celiac arteries with < 180° involvement, (2) venous involvement deemed potentially suitable for reconstruction, and/or (3) biopsy-proven lymph node involvement. Patients with borderline resectable pancreatic cancer were treated with neoadjuvant chemotherapy followed by reimaging and surgery if venous involvement had improved; if disease remained borderline resectable, patients underwent neoadjuvant chemoradiation and surgical exploration as long as reimaging did not reveal evidence of progressive disease. RESULTS: Forty-three patients from October 2013 to April 2017 were diagnosed with borderline resectable pancreatic cancer. Twelve of 42 (29%) patients proceeded to surgical exploration directly after neoadjuvant chemotherapy; 23 (55%) received neoadjuvant chemoradiation. Overall, 28/43 (65%) underwent exploration with 19 (44%) able to undergo resection. Of those, 14/19 (74%) attained R0 resection and 11/19 (58%) were pathologic N0. No pretreatment or treatment variables were associated with resection rates; resection was the only variable associated with survival. CONCLUSION: This report demonstrates the feasibility of implementing a standardized approach to borderline resectable pancreatic cancer across multiple sites over a wide geographic area. Adherence to protocol therapies was good and surgical outcomes are similar to many reported series.

Prophylactic hyperthermic intraperitoneal chemotherapy in patients with epithelial appendiceal neoplasms.

Background Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising approach for preventing peritoneal carcinomatosis in high-risk patients. We report our initial experience with prophylactic HIPEC in a series of patients with appendiceal neoplasms. Methods We retrospectively reviewed our prospectively maintained database to identify patients who underwent HIPEC in the absence of peritoneal disease. Patients with previously documented peritoneal surface disease were excluded. Data regarding clinical, operative and pathological features were analysed. Results Out of 322 HIPEC procedures performed between March 2007and August 2015, we identified 16 patients who underwent surgery with prophylactic intent. Primary diagnoses included high-grade and low-grade appendiceal neoplasms. Most patients presented originally with appendiceal perforation; all patients underwent initial surgery during which the appendix or right colon were resected. Following a median time interval of 2.2 months, a second surgery performed at our institution consisted of completion of omentectomy, partial colectomy and oophorectomy, with administration of prophylactic HIPEC (using mitomycin C). A totally laparoscopic approach was attempted and achieved in 11 patients in whom the median duration of surgery, estimated intraoperative blood loss and length of hospitalisation were 251 min, 100 cm(3) and 4 days, respectively. There were no cases of major perioperative morbidity or mortality. Conclusions Prophylactic HIPEC for appendiceal neoplasms is feasible, safe and may be performed laparoscopically. Larger studies with long-term follow-up are needed to determine whether a survival benefit is associated with this treatment.

Serum hepatitis B surface antigen correlates with tissue covalently closed circular DNA in patients with hepatitis B-associated hepatocellular carcinoma.

Quantitation of hepatitis B surface antigen (HBsAg) in hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains to be clearly defined. This study aims to determine the association of HBsAg quantity with intrahepatic HBV viral load and activity in both tumor and non-neoplastic liver of HBV-HCC patients. Data were obtained from 89 prospectively enrolled patients treated with primary liver resection for HBV-HCC at a single Western institution (2008-2013). Circulating HBsAg was quantitated using ELISA. HBV DNA, covalently closed circular (cccDNA) and precore-pregenomic RNA (preC-pgRNA) in both tumor and non-neoplastic liver were quantitated by real-time PCR from fresh liver resection specimens. Circulating HBsAg was detectable in all 89 patients. HBsAg negatively correlated with age, and positively correlated with pre-operative serum AFP and ALT levels. HBsAg correlated with HBV cccDNA copy number in tumor or non-neoplastic liver tissue. It also correlated with preC-pgRNA copy number in non-neoplastic liver tissue. HBsAg did not correlate with serum HBV DNA, total intrahepatic HBV DNA, viral replicative activity or transcriptional activity. In HBV-HCC patients, HBsAg levels correlated with cccDNA copy number in tumor or non-neoplastic liver tissue, suggesting that a greater pool of cccDNA is associated with a higher rate of HBsAg production.

Outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on patients with diaphragmatic involvement.

PURPOSE: The purpose of this study is to assess the short-term morbidity and mortality in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with diaphragmatic involvement. METHODS: All patients undergoing CRS/HIPEC at a tertiary care institution from April 2007 to October 2013 were retrospectively reviewed. Patients with diaphragmatic disease (Group 1) were compared to those who did not (Group 2). Univariate, propensity score analysis, and multivariate analysis were used to compare groups focusing on postoperative complications. RESULTS: A total of 199 patients underwent CRS/HIPEC. Diagnoses included appendiceal/colorectal cancers (56 %), pseudomyxoma peritoneii (12 %), and gastric cancer (7 %). Group 1 was composed of 89 patients (44.7 %) with diaphragmatic involvement, of which 37.1 % underwent diaphragm stripping and 62.9 % required a full-thickness diaphragmatic resection. Group 1 had longer operative times (p = 0.009), increased transfusion requirements (p = 0.007), less optimal cytoreduction (p = 0.010), longer ICU stay (p = 0.003), and overall hospital stay (p = 0.039). Major complications were significantly higher in Group 1: 26 (29 %) versus 16 (15 %), p = 0.020. Rate of respiratory complications was not different between groups (G1: 14/26, 53.8 % and G2: 6/16, 37.5 %, p = NS). Ninety-day mortality was not significantly different. Diaphragmatic involvement (Estimate 1.235, SE 0.387, p = 0.017) was an independent predictor of 30-day morbidity in patients with <5 organs involved in cytoreduction. CONCLUSIONS: Diaphragmatic involvement is associated with higher tumor burden and more complex operations. It is a strong independent predictor 30-day morbidity in patients with <5 organs involved in cytoreduction. However, perioperative mortality rates are not significantly different between the groups, suggesting that diaphragm stripping or resection is warranted in well-selected patients if it allows for complete cytoreduction.

Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice.

BACKGROUND: Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria. METHODS: To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days. RESULTS: We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic. The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs. CONCLUSION: These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.

Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts).

Unlike melanoma, clear cell sarcoma harbors either a t(12;22)(q13;q12) recurrent translocation, resulting in an EWSR1/ATF1 chimeric gene, or less commonly a t(2;22)(q34;q12) translocation fusing EWSR1 and CREB1. Few studies have examined the prevalence of all chimeric types and variants to assess the usage of ancillary genetic testing in routine diagnosis. We investigated rearrangement prevalence in 17 clear cell sarcomas, two positive control cell lines, and two melanomas (negative controls). Fluorescence in situ hybridization (FISH) analysis using the LSI EWSR1 break-apart probe and a reverse transcription polymerase chain reaction (RT-PCR) assay optimized for formalin-fixed paraffin-embedded tissue to detect all four reported EWSR1/ATF1 clear cell sarcoma chimeric types and the EWSR1/CREB1 variant was performed. All 15 cases available for testing by FISH were positive for EWSR1 rearrangement including two cases with insufficient RNA for RT-PCR. Thirteen of 15 cases successfully tested by RT-PCR harbored a type 1 chimeric transcript (EWSR1 exon 8/ATF1 exon 4), of which five tumors simultaneously carried a type 2 chimeric transcript (EWSR1 exon 7/ATF1 exon 5). One case carried a type 2 transcript alone and one case contained an EWSR1/CREB1 transcript. Both control cases were positive by both techniques with one case carrying both types 1 and 2 chimeric transcripts and the other types 2 and 3 (EWSR1 exon 10/ATF1 exon 5). Consequently, both techniques are equally effective in assessing for an EWSR1 rearrangement and are useful ancillary diagnostic tests for clear cell sarcoma. They also reinforce the prevalence of this translocation in these tumors. In addition, EWSR1-CREB1 was identified in a clear cell sarcoma of soft tissue providing further evidence that this chimeric variant is not exclusive to gastrointestinal clear cell sarcomas and should be included in RT-PCR assays of soft tissue clear cell sarcomas.

Computed tomography scan-driven selection of treatment for retroperitoneal liposarcoma histologic subtypes.

BACKGROUND: Well differentiated (WD) and dedifferentiated (DD) retroperitoneal liposarcoma (RPLS) have distinct biologic behaviors. Consequently, the therapeutic approaches for these tumors differ and mandate an accurate preoperative diagnosis. The authors of this report evaluated whether computed tomography (CT) can be used to differentiate between WD and DD RPLS. METHODS: Imaging studies (CT, magnetic resonance imaging, and positron emission tomography-CT) from 78 patients with RPLS who underwent surgery at the University of Texas M. D. Anderson Cancer Center (UTMDACC) between 2001 and 2007 were reviewed by a senior bone and soft tissue sarcoma radiologist who was blinded to the final histopathologic diagnosis. A focal nodular/water density area within an RPLS was interpreted as a marker suggestive of DD. Correlations between imaging diagnosis, histology, and clinical outcome were analyzed. RESULTS: The study radiologist identified 60 RPLS as DD and 17 RPLS as WD. A radiologic diagnosis of a WD was correlated with preoperative biopsy and postoperative histology in all patients (100%). Focal nodular/water density was a very sensitive marker of DD (97.8%); however, it had relatively low specificity (51.5%). Sixteen WD RPLS (48.5%) contained focal nodular/water density areas, leading to their misdiagnosis as DD; half of those tumors had hypercellular WD. Of 78 preoperative biopsies, 22 (28.2%) were performed at UTMDACC under CT guidance. Preoperative histologic diagnoses obtained from 12 biopsies derived from focal nodular/water density areas were confirmed as unchanged on final pathology; whereas, in 50% of biopsies that were not taken from a suspicious area, DD histology was misdiagnosed as WD. CONCLUSIONS: When CT features are suggestive of WD, no further diagnostic tests are needed for tumor characterization. Moreover, CT can accurately identify most DD, thereby rendering their under-treatment unlikely; however, a CT-guided biopsy is needed to differentiate between DD and WD RPLS that contain focal nodular/water density areas, thereby avoiding their over treatment.

Establishing prognosis in retroperitoneal sarcoma: a new histology-based paradigm.

BACKGROUND: Retroperitoneal sarcoma (RPS) American Joint Committee on Cancer (AJCC) staging applies to primary tumors only; due to specific RPS disease characteristics, staging is driven primarily by grade, stratifying patients into only two distinct prognostic subsets. The objective of this study was to help improve currently available staging for RPS by establishing a new, more robust histology-based prognostic system. METHODS: A RPS database of 1,118 patients seen at our institution (1996-2006) identified 343 patients treated for resectable primary or recurrent disease; a histologic subtype-based RPS prognostic system was designed and evaluated for prognostic accuracy in comparison with the current AJCC staging system. RESULTS: Histology stratified patients into three groups by prognosis (P<0.0002): atypical lipomatous tumor (ALT), non-ALT liposarcoma (LPS), and "other," an improvement compared with AJCC staging which could only identify two distinct prognostic groups. In contrast to AJCC staging, this prognostic stratification was reproducible for both primary and recurrent RPS (P<0.0001). After multivariate analysis, LPS (P=0.0004) and "other" histologies (P<0.0001) were found to be independent predictors of worse survival. The concordance ratio of this model was 0.74, equivalent to that of the model using the AJCC staging system. CONCLUSIONS: A histology-based RPS prognostic system has two advantages over AJCC staging: it can stratify into three versus two distinct prognostic groups, and it can be used for both primary and recurrent RPS. Distinct risk stratification is critical for specific assessment of prognosis as well as decisions regarding individualized adjuvant therapies, hence the advantage of a three-tiered histology-based system applicable in both primary and recurrent RPS.

Specific mutations in the beta-catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors.

Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local invasiveness and relentless recurrence. Molecular determinants of desmoid recurrence remain obscure. beta-Catenin deregulation has been commonly identified in sporadic desmoids although the incidence of CTNNB1 (the gene encoding beta-catenin) mutations is uncertain. Consequently, we evaluated the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from 160 patients, 1985 to 2005) and control dermal scars were assembled into a clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138-sporadic desmoid subset. Immunohistochemical scoring was performed per standard criteria and data were analyzed using Kaplan-Meier and other indicated methods. CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%), 45F (33%), and 45P (8%, excluded from further analysis because of rarity). Five-year recurrence-free survival was significantly poorer in 45F-mutated desmoids (23%, P < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear beta-catenin expression was observed in 98% of specimens and intensity was inversely correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1 mutations are highly common in desmoid tumors. Furthermore, patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches.

Angiogenesis-promoting gene patterns in alveolar soft part sarcoma.

PURPOSE: We examined a cohort of patients with alveolar soft part sarcoma (ASPS) treated at our institution and showed the characteristic ASPSCR1-TFE3 fusion transcript in their tumors. Investigation of potential angiogenesis-modulating molecular determinants provided mechanistic and potentially therapeutically relevant insight into the enhanced vascularity characteristic of this unusual tumor. EXPERIMENTAL DESIGN: Medical records of 71 patients with ASPS presenting at the University of Texas M.D. Anderson Cancer Center (1986-2005) were reviewed to isolate 33 patients with formalin-fixed paraffin-embedded material available for study. RNA extracted from available fresh-frozen and formalin-fixed paraffin-embedded human ASPS tumors were analyzed for ASPSCR1-TFE3 fusion transcript expression using reverse transcription-PCR and by angiogenesis oligomicroarrays with immunohistochemical confirmation. RESULTS: Similar to previous studies, actuarial 5- and 10-year survival rates were 74% and 51%, respectively, despite frequent metastasis. ASPSCR1-TFE3 fusion transcripts were identified in 16 of 18 ASPS samples. In the three frozen samples subjected to an angiogenesis oligoarray, 18 angiogenesis-related genes were up-regulated in tumor over adjacent normal tissue. Immunohistochemistry for jag-1, midkine, and angiogenin in 33 human ASPS samples confirmed these results. Comparison with other sarcomas indicates that the ASPS angiogenic signature is unique. CONCLUSION: ASPS is a highly vascular and metastatic tumor with a surprisingly favorable outcome; therapeutically resistant metastases drive mortality. Future molecular therapies targeting overexpressed angiogenesis-promoting proteins (such as those identified here) could benefit patients with ASPS.