A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases.

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7-/CK20+/CDX2+/PAX8-. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1-50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.

Nuclear ß-catenin and CDX2 expression in ovarian endometrioid carcinoma identify patients with favourable outcome.

AIMS: Ovarian endometrioid carcinoma (EC) generally has a good prognosis. Adjuvant chemotherapy can be spared in low-stage disease, but prognostic biomarkers are needed to refine the treatment threshold. Wnt/ß-catenin signalling is commonly altered in EC. We examined immunohistochemical expression of nuclear ß-catenin and CDX2 as prognostic biomarkers for EC; both are mediators of the Wnt pathway. METHODS AND RESULTS: We evaluated two ovarian EC cohorts, discovery set (n = 183) and validation set (n = 174), with ovarian cancer-specific survival (OCSS) as the primary end-point. In univariable analysis, nuclear ß-catenin expression was significantly associated with longer OCSS in the discovery set [hazard ratio (HR) = 0.36, 95% confidence interval (CI) = 0.16-0.74, P = 0.004] and the validation set (HR = 0.35, 95% CI = 0.11-0.89, P = 0.006). Similar significant associations were observed with CDX2 expression in the discovery set (HR = 0.25, 95% CI = 0.11-0.50, P < 0.001) and validation set (HR = 0.27, 95% CI = 0.07-0.75, P = 0.020). In multivariable analysis, combined positivity of both markers was significantly associated with longer OCSS in the discovery set (HR = 0.20, 95% CI = 0.06-0.49, P < 0.001) and in the validation set (HR = 0.33 95% CI = 0.07-0.1.06, P = 0.047). In a stratified analysis for stage IC/II EC, combined positivity identified a subset of patients with a significantly longer OCSS in the discovery cohort but only a non-significant trend in the validation cohort. CONCLUSIONS: Nuclear ß-catenin and CDX2 expression individually or in combination are validated prognostic markers for ovarian EC. However, their full potential to stratify low risk patients at adjuvant threshold awaits further multimarker study.

Synchronous endometrial and ovarian carcinomas: predictors of risk and associations with survival and tumor expression profiles.

PURPOSE: Synchronous endometrial and ovarian tumors (SEOs) are diagnosed in 10% of ovarian cancer patients. We examined predictors of SEOs, evaluated associations of SEOs with survival and characterized ovarian tumor profiles using immunohistochemistry. METHODS: We included patients with endometrioid (n = 180) and clear cell (n = 165) ovarian carcinoma identified from the Alberta Cancer Registry between 1979 and 2010 for whom we abstracted medical records and constructed tumor tissue microarrays (TMAs). A concurrent diagnosis of endometrial cancer was obtained from the medical chart. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs. Protein expression in ovarian tumors of patients with and without SEOs was evaluated using Fisher's exact test. RESULTS: Comparing 52 patients with SEO tumors to 293 patients with endometrioid or clear cell ovarian carcinomas, endometriosis at the ovary (OR = 0.45, 95% CI = 0.23-0.87, p = 0.02) was the strongest predictor of decreased risk in multivariable models. Premenopausal status (OR = 2.17, 95% CI = 0.92-5.13, p = 0.08) and lower pre-treatment CA125 levels (OR = 0.17, 95% CI = 0.02-1.32, p = 0.09) showed weaker associations. There were no significant differences in survival between patients with or without SEO tumors. More patients with SEO tumors compared to endometrioid ovarian carcinoma were deficient in MLH1, PMS2 and PTEN (p ≤ 0.03). CONCLUSIONS: Endometriosis may not be the mechanism by which SEO cancers arise. Altered tumor oncoprotein expression between women with and without SEOs indicates important biological differences although this did not translate into prognostic differences.

Molecular alterations in indolent, aggressive and recurrent ovarian low-grade serous carcinoma.

AIMS: The clinical courses of patients with low-grade serous carcinoma (LGSC) can be substantially different. The purpose of this study was to explore whether molecular or pathological features could identify patients who follow a more aggressive course. METHODS AND RESULTS: Twenty-six primary LGSCs (11 with an aggressive clinical course, and 15 with an indolent clinical course) and five paired recurrences were assessed for non-synonymous somatic mutations in 18 MAPK pathway genes and in 42 other classic cancer 'hotspot' genes by use of a custom-designed AmpliSeq panel based on the AmpliSeq Cancer hotspot panel v2. Copy number alterations for 94 target genes were assessed with the nCounter v2 Cancer CN assay. Immunohistochemistry for 12 proteins was performed. We detected 16 mutations in 13 of 26 cases (50%), affecting five genes that signal through the MAPK pathway, and one ESR1 mutation implicated in resistance to endocrine therapy in breast cancer. Recurrent samples were concordant with the primary tumour with respect to the mutational status, but all five cases showed additional alterations at the copy number or protein expression level. The absence of progesterone receptor (PR) expression and the presence of myometrial lymphovascular invasion were associated with an unfavourable outcome (log-rank P = 0.016 and P < 0.0001, respectively), but none of the other molecular features assessed showed an association. CONCLUSION: Despite limited case numbers, it appears that current molecular testing is inferior to a pathological parameter or protein expression in predicting the outcome of LGSCs. Prediction of outcome based on the primary tumour may be confounded by additional changes acquired over time.

Immunohistochemical Profiling of Endometrial Serous Carcinoma.

Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%-98%] and specificity of 87.8% (95% CI, 75%-95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%-99%) and specificity of 72.2% (95% CI, 46%-90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%-79%) and specificity of 98.0% (95% CI, 94%-99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.

Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications.

This paper aims to validate whether hormone receptor expression is associated with longer survival among women diagnosed with ovarian endometrioid carcinoma (EC), and whether it identifies patients with stage IC/II tumors with excellent outcome that could be spared from toxic chemotherapy. Expression of estrogen receptor (ER) and progesterone receptor (PR) was assessed on 182 EC samples represented on tissue microarrays using the Alberta Ovarian Tumor Type (AOVT) cohort. Statistical analyses were performed to test for associations with ovarian cancer specific survival. ER or PR expression was present in 87.3% and 86.7% of cases, respectively, with co-expression present in 83.0%. Expression of each of the hormonal receptors was significantly higher in low-grade tumors and tumors with squamous differentiation. Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08-0.42, p = 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10-0.53, p = 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease. However, the five-year ovarian cancer specific survival among women with ER positive stage IC/II EC was 89.0% (standard error 3.3%) and for PR positive tumors 89.9% (standard error 3.2%), robustly below the 95% threshold where adjuvant therapy could be avoided. We validated the association of hormone receptor expression with ovarian cancer specific survival independent of standard predictors in an independent sample set of EC. The high ER/PR co-expression frequency and the survival difference support further testing of the efficacy of hormonal therapy in hormone receptor-positive ovarian EC. The clinical utility to identify a group of women diagnosed with EC at stage IC/II that could be spared from adjuvant therapy is limited.

Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype-specific Lynch syndrome screening in ovarian carcinomas.

AIMS: Lynch syndrome screening in ovarian carcinoma is controversial. The aim of this study was to assess the frequency of deficient mismatch repair (dMMR) protein in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types. METHODS AND RESULTS: Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas, but not in other histological types. Within endometrioid carcinomas, 11 of 25 dMMR cases showed abnormal MLH1/PMS2, 10 cases showed abnormal MSH2/MSH6, and four cases showed only abnormal MSH6, indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three cases and only abnormal MSH6 in one case, all probably related to Lynch syndrome. Within endometrioid carcinomas, dMMR was significantly associated with age <50 years, synchronous endometrial endometrioid carcinoma, a higher CA125 level at diagnosis, higher FIGO grade, absence of ARID1A, and at least 20 CD8-positive intraepithelial lymphocytes per high-power field, but was not associated with cancer-specific death. Age <50 years, higher CA125 levels at diagnosis and at least 20 CD8-positive intraepithelial lymphocytes per high-power field remained significant after adjustment for multiple testing, but their sensitivity for identifying dMMR remained insufficient. CONCLUSION: Our data support the policy of histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas.

Progesterone receptor expression is associated with longer overall survival within high-grade histotypes of endometrial carcinoma: A Canadian high risk endometrial cancer consortium (CHREC) study.

OBJECTIVE: To assess the association of hormone receptor expression with outcome in high-grade endometrial carcinomas. METHODS: This study included three sites participating in the Canadian High Risk Endometrial Cancer (CHREC) consortium. Sections from tissue microarrays containing cases with a diagnosis of endometrioid grade 3 (EC3) and endometrial serous carcinoma (ESC) were assessed for estrogen (ER) and progesterone receptor (PR) expression by immunohistochemistry. Expression was considered present if >1% of tumor cell nuclei were labeled. Associations with overall survival were assessed. RESULTS: ER expression was present in 168/216 (78%) of EC3 and 124/192 (65%) of ESC. PR expression was present in 148/212 (70%) of EC3 and 83/196 (42%) of ESC. PR expression was significantly associated with favorable overall survival in EC3 and ESC (log rank, p=0.018 and p=0.0024) but ER expression was not. PR expression was significantly associated with favorable overall survival in EC3 independent of age, stage, center and lymph-vascular invasion (hazard ratio=0.457, 95% CI 0.257-0.811, p=0.0075) as well as in stage I and II ESC (hazard ratio=0.266, 95% CI 0.094-0.750, p=0.0123). CONCLUSION: Our data provide support for the assessment of the PR expression status in EC3 and ESC. Future work will be required to determine how PR expression may be incorporated into management of patients with EC3 and ESC.

An Immunohistochemical Algorithm for Ovarian Carcinoma Typing.

There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping. A total of 1626 ovarian carcinoma samples from the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type were subjected to a reclassification by comparing the original with the predicted histotype. Histotype prediction was derived from a nominal logistic regression modeling using a previously reclassified cohort (N=784) with the binary input of 8 IHC markers. Cases with discordant original or predicted histotypes were subjected to arbitration. After reclassification, 1762 cases from all cohorts were subjected to prediction models (χ Automatic Interaction Detection, recursive partitioning, and nominal logistic regression) with a variable IHC marker input. The histologic type was confirmed in 1521/1626 (93.5%) cases of the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts. The highest misclassification occurred in the endometrioid type, where most of the changes involved reclassification from endometrioid to high-grade serous carcinoma, which was additionally supported by mutational data and outcome. Using the reclassified histotype as the endpoint, a 4-marker prediction model correctly classified 88%, a 6-marker 91%, and an 8-marker 93% of the 1762 cases. This study provides statistically validated, inexpensive IHC algorithms, which have versatile applications in research, clinical practice, and clinical trials.

Patient and disease characteristics associated with late tumour stage at presentation of cervical cancer in northwestern Tanzania.

BACKGROUND: About two thirds of patients with cervical cancer in Tanzania present with advanced tumor stage, leading to significant morbidity and mortality. We designed a study to determine the factors associated with the late tumour stage at presentation among patients with cervical cancer in Mwanza. METHODS: This cross-sectional study recruited women at Bugando Medical Centre (BMC) with histologically confirmed cervical cancer from November 2013 to April 2014. Patients were recruited serially until the sample size was reached. RESULTS: A total of 202 women with histologically confirmed cervical cancer were recruited. The mean age of the patients was 50.5 ± 13.3 years. The majority of patients (n = 129, 63.9%) were diagnosed with late stage disease (IIB-IVB). Patients also presented with severe anemia (n = 78, 38.6%), urinary tract infections (n = 74, 36.6%), hydronephrosis (n = 43, 21.2%), elevated serum creatinine levels (n = 33, 16.3%), vesicovaginal fistula (VVF), (n = 13, 6.4%), lung metastasis (n = 5, 2.4%), metastasis to the urinary bladder (n = 4, 1.9%), rectovaginal fistula (RVF) (n = 3, 1.4%), liver metastasis (n = 2, 0.9%) and hydroureter (n = 2, 0.9%). In multivariate logistic regression, factors associated with late stage at presentation were attending to alternative health practitioners and lack of personal initiative to seek care to formal health facilities (OR 2.3; 95% CI 1.2-4.2, p = 0.011 and OR 2.0; 95 % CI 1.0-3.8, p = 0.028) respectively. CONCLUSION: Communities should be sensitized to women's empowerment, provide community education on early symptoms of cervical cancer, and the importance of early hospital attendance.

Uterine myometrial mature teratoma presenting as a uterine mass: a review of literature.

BACKGROUND: Teratomas are a germ cell tumors composed of two or more tissues which originate from ectoderm, endoderm or mesoderm. These tumors commonly arise from the ovary although other extragonadal sites can be involved, especially in children. CASE PRESENTATION: We report a case of a 21-year-old female of Sukuma ethnicity from the northern region of Tanzania who presented with abdominal pain and distension, fever, and abnormal vaginal discharge for the previous three weeks. The patient was also lactating for the previous 8 months following cesarean section delivery. Pelvic ultrasound suggested pelvic abscess but after laparotomy and histological analysis of a bulky uterus removed a diagnosis of mature uterine teratoma was confirmed. CONCLUSION: Although it is rare, uterine teratoma should be considered in differential diagnosis to any patient with uterine mass even without typical radiological findings.

Ten-year surgical experiences with penile cancer at a tertiary care hospital in northwestern Tanzania: a retrospective study of 236 patients.

BACKGROUND: Penile cancer is an uncommon malignancy in developed countries, but the incidence is as high as 10% to 20% of all male cancers in some developing countries. There is a paucity of published data on this subject in our setting. This study describes the clinicopathological presentation and treatment outcome of this condition in our environment, and highlights challenges associated with the care of these patients and proffers solutions for improved outcome. METHODS: This was a retrospective study of histologically confirmed cases of penile cancer seen at Bugando Medical Centre between January 2004 and December 2013. RESULTS: There were 236 penile cancer patients representing 2.2% of all male malignancies during the study period. The median age was 47 years with a modal age group of 41 to 50 years. Of the 236 patients, 147 (62.3%) had severe phimosis. The majority of patients (89.8%) were uncircumcised. A history of human papilloma virus (HPV) was reported in 12 (5.1%) cases. One hundred eighty-two (77.1%) patients reported history of cigarette smoking. Seven (6.7%) patients were human immunodeficiency virus (HIV) positive. The majority of the patients (68.6%) presented with Jackson's stages III and IV. Squamous cell carcinoma was the most common histopathological type (99.2%). Lymph node metastasis was recorded in 65.3% of cases, and it was significantly associated with the tumor size, histopathological subtype, histopathological grade, lympho-vascular invasion, positive resection margins, and urethral involvement (P < 0.001). Distant metastasis accounted for 4.2% of cases. The majority of patients (63.1%) underwent partial penectomy. Chemotherapy and radiotherapy were given in 14 (5.9%) and 12 (5.1%) patients, respectively. Complication and mortality rates were 22.0% and 4.2%, respectively. HIV positivity, histopathological stage and grade of the tumor, and presence of metastases at the time of diagnosis were the main predictors of death (P < 0.001). The median length of hospitalization was 14 days. Local recurrence was reported in 12 (5.3%) patients. Data on long-term survivals were not available as the majority of patients were lost to follow-up. CONCLUSIONS: Penile cancer is not rare in our environment. The majority of patients present late with advanced stage of the disease. Early detection of primary cancer at an early stage may improve the prognosis.

Ten-year experience with testicular cancer at a tertiary care hospital in a resource-limited setting: a single centre experience in Tanzania.

BACKGROUND: Testicular cancers constitute major therapeutic challenges in resource-limited countries and still carry poor outcomes. There is a paucity of published data regarding testicular cancer in Tanzania, and Bugando Medical Centre in particular. This study describes the clinicopathological pattern, treatment outcome and challenges in the management of testicular cancer in our local setting. METHODS: This was a retrospective study including all patients who had had histopathologically confirmed testicular cancer at Bugando Medical Centre between February 2004 and January 2014. RESULTS: A total of 56 testicular cancer patients were enrolled in the study, representing 0.9% of all malignancies. The median age of patients at presentation was 28 years, with a peak incidence in the 21-to-30-year age group. A family history of testicular cancer was reported in four (5.4%) patients. A history of cryptorchidism was reported in six (10.7%) patients. Most patients (57.1%) presented late with an advanced stage of cancer. Testicular swelling was the main complaint in 48 (85.7%) patients. The right testis was involved in 67.9% of cases. Lymph node and distant metastases were documented in 10 (17.9%) and 12 (21.4%) patients, respectively. Histologically, 80.4% of patients had germ cell cancers, with seminoma accounting for 62.2% of cases. The most common surgical procedure was inguinal orchidectomy (77.4%). Adjuvant chemotherapy and radiotherapy were used in six (11.1%) and four (7.4%) patients, respectively. Eight (14.3%) patients died. The main predictors of mortality (P<0.001) were patient's age (>65 years), late presentation (>6 months), stage of disease, and presence of metastasis at time of diagnosis. The mean follow-up period was 22 months. At the end of five years, only 18 (37.5%) patients were available for follow-up and the overall 5-year survival rate was 22.2%. The main predictors of 5-year survival rate (P<0.001) were patients' age, stage of disease, and presence of lymph node and distant metastases. CONCLUSIONS: Testicular cancers, though rare in our setting, still carries a poor prognosis. Late presentation, poverty, paucity of resources and the high cost of newer imaging and treatment modalities are major challenges to management. Better health funding and education regarding testicular self-examination is essential.

Hepatocellular carcinoma: clinicopathological profile and challenges of management in a resource-limited setting.

BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries. There is a paucity of published data regarding hepatocellular carcinoma in Tanzania, and the study area in particular. This study describes the clinicopathological profile of hepatocellular carcinoma in our local setting and highlights the challenging problems in the management of this disease. METHODS: This was a retrospective study of histopathologically confirmed cases of hepatocellular carcinoma seen at Bugando Medical Center between March 2009 and February 2013. RESULTS: A total of 142 patients (M: F = 2.2: 1) were studied representing 4.6% of all malignancies. The median age of patients was 45 years. Hepatitis B virus infection (66.2%) and heavy alcohol consumption (60.6%) were the most frequently identified risk factors for hepatocellular carcinoma. The majority of patients (88.0%) presented late with advanced stages. HBsAg was positive in 66.2% of the patients and Hepatitis C Virus antibody in 16.9%. Thirteen (9.2%) patients tested positive for HIV infection. Most patients (52.8%) had both right and left lobe involvement. The trabecular pattern (47.9%) was the most frequent histopathological type. None of patients had curative therapy because of the advanced nature of the disease. Coagulopathy (45.7%) was the most common complications. The overall mortality rate was 46.5% and it was significantly associated with comorbidity, HIV positivity, CD4+ count <200 cells/µl, high histological grade, advanced stage of the tumor, presence of distant metastases at the time of diagnosis, and associated complications (P < 0.001). The overall median duration of hospital stay was 14 days. The majority of patients (71.1%) were lost to follow-up at the end of the follow-up period. CONCLUSIONS: Hepatocellular carcinoma patients in this region are relatively young at diagnosis and the majority of them present late with an advanced stage and high rate of distant metastasis. Lack of awareness of the disease, poor accessibility to healthcare facilities, and lack of screening programs in this region may contribute to advanced disease at the time of diagnosis. There is a need for early detection, adequate treatment, and proper follow-up to improve treatment outcome.

BCMA CAR-T cells in multiple myeloma-ready for take-off?

Although the approval of new drugs has improved the clinical outcome of multiple myeloma (MM), it was widely regarded as incurable over the past decades. However, recent advancements in groundbreaking immunotherapies, such as chimeric antigen receptor T cells (CAR-T), have yielded remarkable results in heavily pretreated relapse/refractory patients, instilling hope for a potential cure. CAR-T are genetically modified cells armed with a novel receptor to specifically recognize and kill tumor cells. Among the potential targets for MM, the B-cell maturation antigen (BCMA) stands out since it is highly and almost exclusively expressed on plasma cells. Here, we review the currently approved BCMA-directed CAR-T products and ongoing clinical trials in MM. Furthermore, we explore innovative approaches to enhance BCMA-directed CAR-T and overcome potential reasons for treatment failure. Additionally, we explore the side effects associated with these novel therapies and shed light on accessibility of CAR-T therapy around the world.

Evaluation of Breast Health Promotion Intervention Among Catholic Nuns in Lake Zone 'Tanzania.

Objective: Despite facing unique barriers, Catholic nuns in Tanzania require accessible breast health promotion. This study explores interventions to empower nuns through knowledge, improved attitudes, and positive practices, ultimately promoting well-being and early detection for better breast cancer outcomes. Materials and Methods: A quasi-experimental design study guided by the Health Belief Model was conducted to monitor the implementation of a breast health intervention program aimed at increasing breast cancer screening knowledge among 385 Catholic nuns aged 20 to over 60 years old within Lake Zone, Tanzania. Data were collected at two-time points: pre-intervention (baseline) and implementation phase intervention (after three months). The intervention consisted of a 2-hour educational session. Participants had opportunities to ask questions and provide feedback. Results: The breast health promotion intervention was well-received by Catholic nuns, with 339 (88%) expressing strong motivation to learn and promote awareness. The training effectively increased knowledge and positive attitudes towards breast cancer screening. Researcher assistants successfully delivered the program, and 354 (92%) of participants expressed interest in continued education and support. The intervention addressed cultural barriers and empowered nuns to take charge of their health, though some challenges remain meanwhile 158 (41%) had limited prior knowledge, 81 (21%) hesitated to discuss breast health due to religious beliefs, and some faced difficulty applying the learnings. Conclusion: Overall, the breast health promotion intervention had a positive outcome on the Catholic nuns' awareness and knowledge of breast health. However, addressing the identified barriers and challenges is crucial to further enhance the intervention's effectiveness and sustainability.

Clinicopathological profile and surgical treatment of abdominal tuberculosis: a single centre experience in northwestern Tanzania.

BACKGROUND: Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. METHODS: A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. RESULTS: Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/µl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. CONCLUSION: Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival.

Relationship between non-Hodgkin's lymphoma and blood levels of Epstein-Barr virus in children in north-western Tanzania: a case control study.

BACKGROUND: Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. METHODS: A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). CONCLUSIONS: BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children.

Sister Mary Joseph's nodule at a University teaching hospital in northwestern Tanzania: a retrospective review of 34 cases.

BACKGROUND: Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome. METHODS: This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics. RESULTS: A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision. CONCLUSION: Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis.

Endoscopic and clinicopathological patterns of esophageal cancer in Tanzania: experiences from two tertiary health institutions.

BACKGROUND: Esophageal cancer is one of the most serious gastrointestinal cancer worldwide, owing to its rapid development and fatal prognoses in most cases. There is a paucity of published data regarding esophageal cancer in Tanzania and the study area in particular. This study was conducted to describe the endoscopic and clinicopathological patterns of esophageal cancer in this part of the world. The study provides baseline local data for future comparison. METHODS: This was a retrospective study of histologically confirmed cases of esophageal cancer seen at Bugando Medical Center and Muhimbili National Hospital between March 2008 and February 2013. Data were retrieved from medical record computer database and analyzed using SPSS computer software version 17.0. RESULTS: A total of 328 esophageal cancer patients were enrolled in the study, representing 25.3% of all malignant gastrointestinal tract tumors. The male to female ratio was 2.2:1. The median age of patients at presentation was 47 years. The majority of patients (86.6%) were peasants coming from the rural areas. Smoking and alcohol consumption were documented in 74.7% and 61.6% of patients respectively. Family history of esophageal cancer was reported in 4.6% of cases. The majority of patients (81.7%) presented late with advanced stage of cancer. Progressive dysphagia and weight loss were the most common presenting symptoms occurring in all patients. The middle third esophagus (58.5%) was the most frequent anatomical site for esophageal cancer followed by lower third (27.4%) and upper third esophagus (10.4%). Squamous cell carcinoma (96.0%) was the most common histopathological type. Adenocarcinoma occurred in 13 (4.0%) patients. TNM staging was documented in only 104 (31.7%) patients. Of these, 102(98.1%) patients were diagnosed with advanced esophageal cancer (Stages III and IV). According to tumor grading, most of tumors were moderately differentiated accounting for 56.1% of cases. Distant metastasis was documented in 43.3% of patients. CONCLUSION: Esophageal cancer is not uncommon in this region and shows a trend towards a relative young age at presentation and the majority of patients present late with advanced stage. There is a need for screening of high-risk populations and detecting esophageal cancer at an early stage in order to improve chances for successful treatment and survival.