Oncological Clearance Following Resection of the Carcinoma Rectum: A Comparison between Laparoscopic and Open Anterior Resection.

Till the day the rectal cancer deaths in the world is in eighth position. For rectal cancer surgery, short-term benefits are expected to be similar for laparoscopic resection of rectum (LRR) and open resection of rectum (ORR). In Bangladesh though the rectal cancer is the sixteenth most common cause of cancer deaths, there is lack of data regarding outcomes of laparoscopic and open surgical approaches for carcinoma rectum. Purpose of study was to compare oncopathological outcomes by quality of surgical resection between LRR and ORR groups. The quasi experimental study was conducted among 46 subjects who attended in the Department of Colorectal Surgery, Bangabandhu Sheikh Mujib Medical University, Bangladesh from July 2020 to June 2021 with rectal adenocarcinoma within 15cm from the anal verge. Equal number of subjects were allocated for LRR and ORR group. Oncopathological end points such as circumferential resection margin (CRM), distal resection margin (DRM), lymph nodes and quality of mesorectal excision were assessed and compared. Here every patients have given their written consent for this study. Mean age of the subjects for LRR and ORR were 45.47±12.66 and 44.47±12.48 years respectively. Majority of the subjects were in age above 40 years (67.0%). The proportion of male (56.5%) were higher than those of female (43.5%). The complete resection was better in LRR (91.3%) than ORR (87.0%) group though statistically not significant. CRM was lower in LRR (0.0%) than ORR (13.0%) group in respect of frequency distribution. DRM was negative for both LRR and ORR group (95.7% each) and it was not statistically significant. ORR met the National Comprehensive Cancer Network (NCCN) criteria of harvesting 12 lymph nodes were as in LRR group 10 lymph nodes were harvested. The mean harvested lymph nodes were 12.2±5.55 and 10.1±5.55 in LRR and ORR group respectively. The study demonstrated that LRR is better (though statistically not significant) in respect of complete resection and CRM while in harvesting lymph nodes, ORR met the NCCN criteria but LRR does not. There is no difference observed regarding DRM in both groups. On oncopathological point of view both the group showed almost equally effective results. Laparoscopic surgery can be opted as the standard operative technique for surgical management of rectal cancer.

Melanoma and CLL co-occurrence and survival: role of KC history.

BACKGROUND: Survival following melanoma and chronic lymphocytic leukemia (CLL) have both been individually associated with previous history of non-melanoma skin cancers (specifically keratinocyte carcinomas [KC]). Furthermore, melanoma and CLL have been reported to occur within the same patients. The survival experience of patients with both cancers is understudied, and the role of history of KC is unknown. Additional research is needed to tease apart the independent associations between KC and CLL survival, KC and melanoma survival, and the co-occurrence of all three cancers. METHODS: A retrospective cohort study was conducted among patients who were diagnosed with melanoma and/or CLL at a comprehensive cancer center between 2008 and 2020. Multivariable Cox regression models were used to examine the association between history of KC and survival following melanoma and/or CLL with careful consideration of calendar year of diagnosis, treatment regimens and other risk factors. A nested case-control study comparing patients with both CLL and melanoma to those with only CLL or only melanoma was conducted to compare blood parameters across the three groups. RESULTS: A time-dependent association was observed between history of KC and favorable melanoma survival within 4 years following diagnosis and poorer survival post 7 years after melanoma diagnosis. History of KC was not significantly associated with survival following the diagnosis of CLL, after adjustment for clinical factors including historical/concurrent melanoma. Patients with co-occurring melanoma and CLL tended to be diagnosed with melanoma first and had elevated blood parameters including white blood cell and lymphocyte counts as compared with patients who were diagnosed with only melanoma. CONCLUSIONS: History of KC was an independent predictor of survival following melanoma but not of CLL. Additional studies are needed to determine if blood parameters obtained at the time of melanoma diagnosis could be used as a cost-effective way to identify those at high risk of asymptomatic CLL for the promotion of earlier CLL diagnosis.

Pathologic Nodal Staging Before SBRT for Early-stage NSCLC Does Not Impact Overall Survival: A Propensity Score-matched NCDB Analysis.

OBJECTIVE: Stereotactic body radiation therapy (SBRT) for early-stage non-small cell carcinoma of the lung (NSCLC) is increasingly utilized. We sought to assess overall survival (OS) for early-stage NSCLC patients receiving SBRT depending on staging method. METHODS: Early-stage NSCLC patients treated with definitive SBRT were identified in the National Cancer Database (NCDB), and OS was determined based on method of staging. Patient, disease, and treatment characteristics were also analyzed. RESULTS: A total of 12,106 patients were included; 865 (7%) received invasive staging (nodal sampling, NS) and 11,241 (93%) had no nodal sampling (NNS). From this larger dataset, a propensity score matching (1:1 without replacement) was performed, which yielded 839 patients for each group (NNS and NS). With a median follow-up time of 3.12 years, median survival for all patients included in the matched dataset was 2.75 years (95% CI: 2.55-2.93 y), with 2- and 5-year OS estimated at 63.9% and 25.7%, respectively. In a multivariable analysis on matched data, there was no difference in mortality risk between the NNS and NS groups (hazard ratio=1.08, 95% CI: 0.94-1.24, P =0.25). Negative prognostic factors identified in the multivariable analysis of the matched data included: age more than 65, male sex, Charlson-Deyo Score ≥1, and tumor size ≥3 cm. CONCLUSIONS: SBRT use in early-stage NSCLC steadily increased over the study period. Most patients proceeded to SBRT without nodal staging, conflicting with National Comprehensive Cancer Network (NCCN) guidelines which recommend pathologic mediastinal lymph node evaluation for all early-stage NSCLC cases, except stage IA. Our findings suggest similar OS in patients with early-stage NSCLC treated with SBRT irrespective of nodal staging. Furthermore, we highlight patient-related, disease-related, and treatment-related prognostic factors to consider when planning therapy for these patients.

Outcomes for Colorectal Cancer Cases With Peritoneal Metastases Treated With Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy: A Comparative Analysis of Survival Between Peritoneal Carcinomatosis Scores - PCI in a Single Centre.

BACKGROUND/AIM: Peritoneal cancer index (PCI) has been a strong indicator of prognosis for patients receiving cytoreductive surgery. The aim of this single institution study was to compare the survival of peritoneal carcinoma cases treated with cytoreduction surgery arising from colorectal cancer grouped by PCI scores. PATIENTS AND METHODS: A retrospective study of a prospective dataset maintained from 2000 till September 2022, for peritoneal metastases from colorectal cancers was carried out. Of the total of 1,625 peritoneal metastases cases, 415 were identified with colorectal cancer and considered for analysis. Survival was followed for 60 months since the index-peritonectomy for cases in this study. RESULTS: Hazard ratio for 5-year survival using the Cox regression analysis over time (t) with a Log-rank (Mantel-Cox) test for significance between the groups indicated, <15 vs. 15 (HR=2.121, p=0.0338), <15 vs. 16-20 (HR=2.748, p<0.0001), <15 vs. >20 (HR=3.158, p<0.0001), 15 vs. 16-20 (HR=1.262, p=0.5658), 15 vs. >20 (HR=1.566, p=0.2771) and for PCI category 16-20 vs. >20 (HR=1.204, p=0.5355) for survival. Median survival for the categories of PCI <15, PCI-15, PCI-16-20, and PCI >15 was 43.967 (95%CI=28.31-59.63), 20.67 (95%CI=5.01-36.33), 19.50 (95%CI=3.84-35.16), and 14.30 (95%CI=1.36-29.96), respectively. CONCLUSION: A correlation of PCI with survival was confirmed in this study reinforcing the need for assessment of PCI at surgery to help prognostication. Detecting synchronous peritoneal metastases early and prompt treatment can help prevent recurrence and increase survival.

Cytoreduction and HIPEC for Gastric Carcinomatosis: Multi-institutional Analysis of Two Phase II Clinical Trials.

INTRODUCTION: There are no approved locoregional therapies for peritoneal carcinomatosis from gastric adenocarcinoma (GA). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents a potential treatment for advanced GA with isolated peritoneal metastasis. PATIENTS AND METHODS: Two separate single-institution phase II, single-arm studies evaluating CRS-HIPEC using cisplatin with mitomycin C (NIH: NCT03092518, MDACC: NCT02891447) in patients with GA and confirmed peritoneal metastasis were analyzed. The primary endpoint of each trial was overall survival (OS). Clinical, pathologic, and treatment variables were analyzed for association with outcomes. RESULTS: Over 4 years, 41 patients with peritoneal carcinomatosis from GA underwent CRS-HIPEC. All patients had synchronous peritoneal metastasis and received systemic chemotherapy as front-line therapy. A total of 23 patients also received laparoscopic HIPEC prior to open CRS-HIPEC. The majority (63%, n = 26) were male, and median PCI score at CRS-HIPEC was 2. Median OS was 24.9 months from diagnosis and 14.4 months from CRS-HIPEC. Three-year OS was 25% from diagnosis and 22% from CRS-HIPEC. Median RFS was 7.4 months. The rate of 30-day Clavien-Dindo grade ≥ 3 complications was 32%; specifically, the rate of anastomotic leak was 22%. Multivariable analysis identified the number of pathologically positive lymph nodes as an independent predictor of postoperative OS. CONCLUSIONS: In patients with gastric adenocarcinoma and isolated peritoneal metastasis treated with CRS-HIPEC, 3-year OS was 22% from CRS-HIPEC, and complications were common. The number of pathologic lymph node metastases was inversely correlated with overall survival. Further investigation of CRS-HIPEC for GA should include patient selection based on response to systemic chemotherapy or incorporate novel intraperitoneal treatment strategies.

Mesenchymal Stem Cells and Selenium Nanoparticles Synergize with Low Dose of Gamma Radiation to Suppress Mammary Gland Carcinogenesis via Regulation of Tumor Microenvironment.

Breast cancer is one of the most prevalent and deadliest cancers among women in the world because of its aggressive behavior and inadequate response to conventional therapies. Mesenchymal stem cells (MSCs) combined with green nanomaterials could be an efficient tool in cell cancer therapy. This study examined the curative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) with selenium nanoparticles (SeNPs) coated with fermented soymilk and a low dose of gamma radiation (LDR) in DMBA-induced mammary gland carcinoma in female rats. DMBA-induced mammary gland carcinoma as marked by an elevation of mRNA level of cancer promoter genes (Serpin and MIF, LOX-1, and COL1A1) and serum level of VEGF, TNF-α, TGF-ß, CA15-3, and caspase-3 with the reduction in mRNA level of suppressor gene (FST and ADRP). These deleterious effects were hampered after treatment with BM-MSCs (1 × 106 cells/rat) once and daily administration of SeNPs (20 mg/kg body weight) and exposure once to (0.25 Gy) LDR. Finally, MSCs, SeNPs, and LDR notably modulated the expression of multiple tumor promoters and suppressor genes playing a role in breast cancer induction and suppression.

Incidence and associated factors for incidental prostate cancer among patients who underwent surgery for benign prostatic hyperplasia: first report from Somalia.

BACKGROUND: The incidence rate of incidental prostate cancer (IPC) differs significantly among the reported studies in the relevant literature. There is a scarcity of studies regarding IPC reported from Sub-Saharan African Countries, including Somalia. The present is the first study that evaluates the incidence and associated factors for IPC among patients who had surgery for benign prostatic hyperplasia at a tertiary hospital in Somalia. METHOD: This retrospective study reviewed the data of 538 patients with benign prostate hyperplasia, 464 patients who underwent transurethral resection of the prostate (TURP), and 74 patients with open prostatectomy (OP) over 5 years. A binary logistic regression model was used to investigate the association between perioperative factors such as age, prostate volume, total prostate-specific antigen (TPSA) levels, type of surgery, specimen weight, and the finding of IPC. RESULTS: IPC was detected in 17.6%, 18.3% of TURP, and 13.5% of OP patients (p = 0.002). The mean age of the patients was 71.82 ± 7.4; IPC patients had a significantly higher mean age than the BPH group (74 ± 10.9 vs. 71.3 ± 10.8, p < 0.001). Sixty-two percent of the patients were T1b, while 57.8% had ISUP grade groups 1 and 2. Patients with T1a had significantly higher International Society of Urological Pathology (ISUP) grades 1 and 2 than those with T1b (69.4% in T1a vs. 50.8% in T1b, p < 0.001). Increased age, higher TPSA levels, low prostate volume, and specimen weight were independently associated with the finding of incidental prostate carcinoma (OR 1.978, 95% CI 0.95-1.60, P < 0.04; OR 1.839, 95% CI 0.99-2.02, P < 0.001; OR 1.457, 95% CI 0.7102.99, P < 0.001, OR 0.989, 95% CI 1.07-2.94, P = 0.01). IPC was most commonly managed by active surveillance (54.7%), followed by androgen deprivation therapy in 28.4%. The overall survival rate for a 5-year follow-up in the entire cohort was 79%. The cancer-specific mortality was 8.4%. CONCLUSION: The study findings revealed a higher incidence and cancer-specific mortality rate of incidental prostate carcinoma. T1b stage, higher ISUP grade, older age, and higher preoperative TPSA were significantly associated with the overall mortality and cancer-specific mortality rate. More than half of the cases were managed by active surveillance, and it is a safe management strategy, particularly in low-income countries like Somalia.

The significance of the extent of tissue embedding for the detection of incidental prostate carcinoma on transurethral prostate resection material: the more, the better?

The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium-aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1-38) vs. a median of 15 (range 2-74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.

An Update on the Molecular and Clinical Characteristics of Apocrine Carcinoma of the Breast.

Apocrine carcinoma of the breast is a rare malignancy. According to 2019 WHO classification, apocrine cellular features and a characteristic steroid receptor profile (Estrogen receptor (ER)-negative and androgen receptor (AR)-positive) define apocrine carcinoma. Her-2/neu protein expression is reported in ∼30-50% of apocrine carcinomas, while NGS analysis showed frequent PIK3CA/PTEN/AKT and TP53 mutations Followed by deregulation in the mitogen-activated protein kinase pathway components (mutations of KRAS, NRAS, BRAF). A recent miRNA study indicates various miRNAs (downregulated hsa-miR-145-5p and upregulated 14 miRNAs such as hsa-miR-182-5p, hsa-miR-3135b, and hsa-miR-4417) may target the commonly altered pathways in apocrine carcinomas such as ERBB2/HER2 and mitogen-activated protein kinase signaling pathway. Although AR expression is a hallmark of apocrine carcinoma, little is known regarding the efficacy/resistance to antiandrogens. Success of bicalutamide, a non-steroidal anti-androgen, was reported in a case of Her2-negative apocrine carcinoma. Two recent studies, however, described presence of anti-androgen resistance biomarkers (a splice variant ARv7 and AR/NCOA2 co-amplification) in a subset of AR+ apocrine carcinomas, cautioning the use of anti-androgens in AR+ triple-negative breast carcinomas. Apocrine carcinomas rarely show biomarkers predictive of response to immune checkpoint inhibitors (PD-L1 expression, MSI-H status, and TMB-high). Therefore, a comprehensive cancer profiling of apocrine carcinomas is necessary to identify potential therapeutic targets for a truly individualized treatment approach.

Clear Cell Carcinoma (CCC) of the Cervix Is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome: A Comprehensive Analysis of 58 Cases.

Cervical clear cell carcinoma (CCC) is a rare human papillomavirus-independent adenocarcinoma. While recent studies have focused on gastric-type endocervical adenocarcinoma (GTA), little is known about CCC. A total of 58 (CCCs) were collected from 14 international institutions and retrospectively analyzed using univariable and multivariable methods and compared with 36 gastric-type adenocarcinomas and 173 human papillomavirus-associated (HPVA) endocervical adenocarcinoma (ECA) regarding overall survival (OS) and recurrence-free survival (RFS). Most cases were FIGO stage I (72.4%), with Silva C pattern of invasion (77.6%), and the majority were treated with radical surgery (84.5%) and adjuvant therapy (55.2%). Lymphovascular invasion was present in 31%, while lymph node metastasis was seen in 24.1%; 10.3% were associated with abdominopelvic metastases at the time of diagnosis; 32.8% had recurrences, and 19% died of disease. We did not find statistically significant differences in OS and RFS between CCC and GTA at 5 and 10 years (P=0.313 and 0.508, respectively), but there were significant differences in both OS and RFS between CCC and HPVA ECA (P=0.003 and 0.032, respectively). Also, OS and RFS in stage I clear cell and GTA were similar (P=0.632 and 0.692, respectively). Multivariate analysis showed that OS is influenced by the presence of recurrence (P=0.009), while RFS is influenced by the FIGO stage (P=0.025). Cervical CCC has poorer outcomes than HPVA ECA and similar outcomes to human papillomavirus-independent GTA. Oncologic treatment significantly influences RFS in univariate analysis but is not an independent prognostic factor in multivariate analysis suggesting that alternative therapies should be investigated.

Anticancer and antimutagenic activity of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. against skin cancer induced by DMBA: In vitro and in vivo models.

The current study investigated the prospective effect of Silybum marianum L. and Eucalyptus camaldulensis Dehnh extracts against skin cancer. Skin cancer was induced by 7,12-dimethylbenz(a) anthracene (DMBA) in young Balb/c mice. Plant extracts were administered to animals orally, once/day (100mg/kg, 5 days/week) for the 20 weeks. Anticancer activity was examined via tumor progression, where antimutagenic activity was measured using 8-OHdG and sister chromatid exchange (SCE) levels. Eucalyptus camaldulensis Dehnh. leaves extract and Silybum marianum L. leaves extract significantly reduced 8-OHdG in cultured human lymphocytes in a dose-response manner (P<0.05). Similarly, the leave extracts of both plants significantly reduced chromosomal damage as measured by SCE levels (P<0.05). In the skin painting assay, the leave extracts of both plants significantly delayed the onset of tumors compared to DMBA treated group (P<0.05). The Silybum marianum leaves extract significantly reduced tumor incidence (P<0.01) and papilloma frequency (P<0.01) induced by DMBA. The Eucalyptus camaldulensis leaves extract significantly reduced the number of tumors per animal (P<0.05) and incidence of tumors (P<0.001). The in vitro and in vivo findings showed that leaves of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. extracts might be a promising source for anticancer and antimutagenic agents against human cancer.

Flexible endoscopic laser surgery for early glottic carcinoma.

OBJECTIVE: Flexible endoscopic laser surgery (FELS) is able to overcome some limitations of traditional transoral CO2 laser surgery. The objective of this study was to assess the efficacy of FELS in the treatment of T1-T2 glottic carcinoma. METHODS: We applied FELS for 120 patients with T1-T2 glottic carcinoma. Tumour ablation was performed with Nd:YAG laser. In 76 (63.3%) cases the intervention was performed under local anesthesia. Twenty nine (24.2%) patients (T1b - 2, T2-27) underwent postoperative radiation therapy (RT). RESULTS: Successful treatment, with local control and larynx preservation, was obtained in 106 cases (88.3%), with mean follow-up of 6.4 years. More than 50% of the patients were followed-up over 5 years. CONCLUSIONS: FELS can be proposed as an alternative treatment method for patients with early glottic carcinoma. The advantages of the method include: possibility of applying treatment under local anesthesia, that allows avoiding of general anesthesia and its related risks; applicability to patients with contraindications to general anesthesia and patients with anatomic particularities, that make transoral microsurgery impossible, allowing avoidance of the laryngofissure and tracheotomy.

Multidisciplinary management of patients with pubic osteomyelitis, a rare but serious complication after surgery and radiation therapy for advanced gynaecological cancer.

Pubic osteomyelitis is a rare and often late-onset complication of radiation therapy and surgery for vulvar and vaginal carcinoma. It typically presents with vulvar pain, fever, vaginal discharge and/or gait disorders. Pubic osteomyelitis is often accompanied by fistulas or wound dehiscence in the pelvic area. Its accurate diagnosis and treatment are challenging and require a multidisciplinary team effort. In our patients, multiple combined surgical procedures, long-term antibiotic treatment and days to weeks of hospital admission were necessary to treat pubic osteomyelitis. We emphasise the importance of timely and adequate diagnosis and multidisciplinary approach resulting in a course of treatment that is as effective as possible, limiting the impact on quality of life, which is generally high in this group of patients.

Multifunctional Theranostic Graphene Oxide Nanoflakes as MR Imaging Agents with Enhanced Photothermal and Radiosensitizing Properties.

The integration of multiple therapeutic and diagnostic functions into a single nanoplatform for image-guided cancer therapy has been an emerging trend in nanomedicine. We show here that multifunctional theranostic nanostructures consisting of superparamagnetic iron oxide (SPIO) and gold nanoparticles (AuNPs) scaffolded within graphene oxide nanoflakes (GO-SPIO-Au NFs) can be used for dual photo/radiotherapy by virtue of the near-infrared (NIR) absorbance of GO for photothermal therapy (PTT) and the Z element radiosensitization of AuNPs for enhanced radiation therapy (RT). At the same time, this nanoplatform can also be detected by magnetic resonance (MR) imaging because of the presence of SPIO NPs. Using a mouse carcinoma model, GO-SPIO-Au NF-mediated combined PTT/RT exhibited a 1.85-fold and 1.44-fold higher therapeutic efficacy compared to either NF-mediated PTT or RT alone, respectively, resulting in a complete eradication of tumors. As a sensitive multifunctional theranostic platform, GO-SPIO-Au NFs appear to be a promising nanomaterial for enhanced cancer imaging and therapy.

Role of SMARCA4 (BRG1) and SMARCB1 (INI1) in Dedifferentiated Endometrial Carcinoma With Paradoxical Aberrant Expression of MMR in the Well-Differentiated Component: A Case Report and Review of the Literature.

INTRODUCTION: Dedifferentiated endometrial carcinoma is an uncommon highly aggressive uterine tumor. It comprises 2 components: a well-differentiated, low-grade epithelial carcinoma and an undifferentiated carcinoma. The undifferentiated carcinoma frequently exhibits rhabdoid cytologic features. Many of these tumors are characterized by an aberrant switch/sucrose non-fermenting (SWI/SNF) complex. They may also exhibit aberrant expression of mismatch repair (MMR) proteins. Together, these play an important role in the pathogenesis and aggressive nature of the tumor. MATERIAL AND METHODS: We present a case of dedifferentiated endometrial carcinoma in a 63-year-old female showing loss of expression of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4/BRG1), and aberrant expression of MMR proteins. We also review the literature starting from the earliest recognition of this entity and the various studies done to explain its molecular pathogenesis and prognostic importance. RESULTS AND CONCLUSIONS: Recognition of SWI/SNF complex-deficient dedifferentiated endometrial carcinoma is important as these tumors do not respond to platinum-based chemotherapy, and consideration of alternative therapies is often necessary. We also want to emphasize that though most of the studies have found MMR deficiency in the undifferentiated carcinoma component, it may be seen only in the low-grade, well-differentiated component, as observed in this case.

Seven cases of parathyroid carcinoma and review of the literature.

Parathyroid cancer is a rare malignancy and an uncommon cause of hyperparathyroidism. In the present study, we present seven cases of parathyroid carcinoma. The female ratio was 5/7 (71.4%). Median age at diagnosis was 47 years, and median follow-up duration was 60 months (IQR 29-75). Mean calcium level at diagnosis was 12.7 mg/dL (range, 11.3-13.9), and mean parathormone level was 1115 ng/L (IQR 287-1470). Two patients (28.5%) had a palpable neck mass. Coexisting brown tumor was present in three patients (42.8%), and nephrolithiasis was found in one patient (14.2). Average tumor size was 29 mm (IQR 28-40). Capsular and vascular invasion were detected in six patients (85.7%), intrathyroidal spread was observed in two patients (28.5%), and soft tissue invasion was seen in three patients (42.8%). Parathyroid adenoma was present in one patient and parathyroid gland hyperplasia in another patient. Adjuvant radiotherapy was given to four patients (57.1%). There was no metastatic disease or death. At the last visit, two patients had increased parathormone levels and no additional focus could be detected in either. Patients with markedly elevated parathormone and calcium levels and a palpable larger mass on the neck should be evaluated for parathyroid cancer. En bloc resection is the mainstay treatment. Despite contradictory results, adjuvant radiotherapy to the neck may help to reduce the risk of local recurrence in patients with microscopic residual parathyroid carcinoma.

Anti-proliferative activities of coumarins from the Thai medicinal plant Mammea siamensis (Miq.) T. Anders. against human digestive tract carcinoma cell lines.

Geranylated coumarins named mammeasins G-J (1-4) were isolated from the methanol extract of the flowers of Mammea siamensis (Miq.) T. Anders. (Calophyllaceae) originating in Thailand. Their structures were established based on detailed spectroscopic analyses. The isolates, including previously reported coumarin constituents (5-28), exhibited anti-proliferative activities against human carcinoma cell lines HSC-2, HSC-4, MKN-45, and MCF-7. Mammeasin A (7, IC50 = 13.6 µM) and surangin B (15, 15.2 µM), both consisting of the geranyl group, were found to show relatively strong activities against HSC-4 cells and their mechanisms of action were found to involve apoptotic cell death.

Parathyroid Carcinoma: A Single-Institution Experience with an Emphasis on Histopathological Features.

Parathyroid carcinoma (PC) is a rare malignancy that poses a diagnostic challenge on histologic examination. We analyzed various clinicopathologic features of PC. Pathology reports and slides were reviewed to evaluate the diagnostic histopathologic features of archived cases of PC from the years of 2004-2018. The study cohort comprised twenty cases of PC. The median age was 49 years (range 21-73 years) with equal gender distribution (M:F = 1:1). Most patients presented with symptoms of hypercalcemia (n = 7, 54%). Serum calcium and serum parathyroid hormone were elevated in all but one patient. The right inferior parathyroid was commonly involved (n = 8/14, 57%). The mean tumor size was 2.4 cm (range 0.8-3.5 cm). On frozen section examination, PC was diagnosed in 8 out of 9 cases. Vascular (n = 19/20, 95%) and soft tissue invasion (n = 10/20, 50%) were the most common characteristic histologic findings. Capsular invasion was identified in all cases. Perineural invasion or metastasis at presentation was absent in all cases. Other histological features noted were intratumoral fibrous bands (70%), nodular growth pattern (70%), moderate nuclear atypia (30%), prominent nucleoli (20%), and necrosis (20%). Regional lymph nodes were negative for metastatic disease in all cases (n = 10). Eight out of 16 patients received adjuvant radiotherapy. Follow-up was available in 16 cases (median 21.5 months). Two patients died of disease. Vascular and soft tissue invasion are the most common diagnostic histologic features of PC. Capsular invasion is important to distinguish PC from its benign counterparts. Intraoperative frozen section examination can be used for accurate diagnosis and surgical management.

Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial.

BACKGROUND: It is unknown whether dietary supplementation with vitamin D or calcium prevents keratinocyte carcinomas, also known as nonmelanoma skin cancers. OBJECTIVES: This study aimed to determine whether daily vitamin D or calcium supplementation alters the risk of basal cell carcinoma (BCC) or invasive cutaneous squamous cell carcinoma (SCC). METHODS: The Vitamin D/Calcium Polyp Prevention Study is a completed multicenter, double-blind, placebo-controlled, partial 2 × 2 factorial, randomized clinical trial of vitamin D, calcium, or both for the prevention of colorectal adenomas. During 2004-2008, a total of 2259 men and women, 45-75 y of age, recently diagnosed with a colorectal adenoma, were randomly assigned to 1000 IU/d of vitamin D3 or placebo and 1200 mg/d of calcium carbonate or placebo for 3 or 5 y, and followed after treatment ended. Reports of incident BCC or SCC were confirmed from pathology records. RESULTS: During a median follow-up of 8 y, 200 (9%) participants were diagnosed with BCC and 68 (3%) participants were diagnosed with SCC. BCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.96; 95% CI: 0.73, 1.26), calcium compared with no calcium (HR: 1.01; 95% CI: 0.74, 1.39), and both agents compared with neither (HR: 0.99; 95% CI: 0.65, 1.51). SCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.79; 95% CI: 0.49, 1.27), but there was suggestive evidence of beneficial treatment effects for calcium compared with no calcium (HR: 0.60; 95% CI: 0.36, 1.01) and both agents compared with neither (HR: 0.42; 95% CI: 0.19, 0.91). CONCLUSIONS: Calcium alone or in combination with vitamin D may reduce the risk of SCC, but not BCC. This trial was registered at clinicaltrials.gov as NCT00153816.

Generation and testing of engineered multimeric Fabs of trastuzumab.

Recombinant antibodies fragments in several new formats are routinely investigated and used in diagnostic and therapeutic applications as anti-cancers molecules. New antibody formats are generated to compensate the need for multispecificity and site-specific introduction of fluorescent dyes, cytotoxic payloads or for generating semisynthetic multimeric molecules. Fabs of trastuzumab bearing transglutaminase (MTG) reactive sites were generated by periplasmic expression in E. coli and purified. Multimeric Fabs were generated by either disulfide bridge formation or by using MTG-sensitive peptide linkers. Binding to receptor was assessed by ELISA and SPR methods. Internalization and growth inhibition assays were performed on BT-474 and SKBR3 Her2+ cells. Fabs were successfully produced and dimerized or trimerized using MTG and suitably designed peptide linkers. Site-specific derivatizations with fluorophores were similarly achieved. The monomeric, dimeric and trimeric variants bind the receptor with affinities similar or superior to the full antibody. Fab and Fab2 are rapidly internalized in Her2+ cells and exhibit growth inhibition abilities similar to the full antibody. Altogether, the data show that the recombinant Fabs can be produced in E. coli and converted into multimeric variants by MTG-based bioconjugation. Similar approaches are extendable to the introduction of cytotoxic payloads for the generation of novel Antibody Drug Conjugates.