Gastrosplenic fistula due to splenic lymphoma: two case reports and review of the literature.

BACKGROUND: Gastrosplenic fistula is a rare and potentially fatal complication of various conditions. Lymphoma is the most common cause. It can occur spontaneously or after chemotherapy. Gastrosplenic fistula diagnosis can be confused with a splenic abscess because of the presence of air into the mass. The computed tomography identification of the fistulous tract is the key to a right diagnosis. Treatment modalities include surgical resection, chemotherapy, or a combination of both. CASE PRESENTATION: Here we report two patients with gastrosplenic fistula due to diffuse large B cell lymphoma. The first patient was a 54-year-old Caucasian woman with an enormous primary splenic diffuse large B cell lymphoma leading to the development of a spontaneous fistula in the stomach. The second patient was a 48-year-old Caucasian male patient with an enormous splenic diffuse large B cell lymphoma complicated by fistula after chemotherapy. Both patients died of septic shock several days after surgery. CONCLUSION: Gastrosplenic fistula is a rare complication with a poor-prognosis, for which surgery is currently the preferred treatment.

Immune checkpoints as potential theragnostic biomarkers for epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. EOC is asymptomatic in early stages, so most patients are not diagnosed until late stages, highlighting the need to develop new diagnostic biomarkers. Mediators of the tumoral microenvironment may influence EOC progression and resistance to treatment. AIM: To analyze immune checkpoints to evaluate them as theranostic biomarkers for EOC. PATIENTS AND METHODS: Serum levels of 16 immune checkpoints were determined in EOC patients and healthy controls using the MILLIPLEX MAP® Human Immuno-Oncology Checkpoint Protein Magnetic Bead Panel. RESULTS: Seven receptors: BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2 are differentially expressed between EOC and healthy controls. Serum levels of immune checkpoints in EOC patients are positively significantly correlated with levels of their ligands, with a higher significant correlation between CD80 and CTLA4 than between CD28 and CD80. Four receptors, CD40, HVEM, PD-1, and PD-L1, are positively associated with the development of resistance to Taxol-platinum-based chemotherapy. All of them have an acceptable area under the curve (>0.7). CONCLUSION: This study has yielded a first panel of seven immune checkpoints (BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2) associated with a higher risk of EOC and a second panel of four immune checkpoints (CD40, HVEM, PD-1, PD-L1) that may help physicians to identify EOC patients who are at high risk of developing resistance to EOC chemotherapy.

Pathologic complete response to neoadjuvant imatinib of a gastric stromal tumor with concomitant mutations in KIT: A case report and literature review.

Key clinical message: We report the first case of pathologic complete response (pCR) to neoadjuvant imatinib in a gastric stromal tumor harboring KIT mutations in both exons 11 and 9. The significance of this co-occurrence is unknown and might increase the responsiveness of gastrointestinal stromal tumors (GISTs) to imatinib. Abstract: pCR of GIST to neoadjuvant imatinib is rare. We report a case of pCR to neoadjuvant imatinib in a gastric stromal tumor that harbored co-occurrence of multiple KIT mutations in exons 11 and 9. This co-occurrence in exons 9 and 11 is the first to be reported in the English literature.

Identification of two theranostic biomarker panels for epithelial ovarian cancer.

BACKGROUND: Epithelial Ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. Because the disease is asymptomatic in early-stage, the majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Mediators of tumoral microenvironment may affect EOC progression and resistance to treatment. AIM OF THE STUDY: Analysis of serum proteins to identify a panel of theranostic biomarkers for EOC. PATIENTS AND METHODS: Serum levels of 65 analytes were determined in EOC patients, and healthy controls with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. RESULTS: Twenty-one analytes: 7 cytokines (IFN-γ, IL-12p70, IL-13, IL-18 and TSLP), 7 chemokines (Eotaxin, eotaxin-2, IP-10, BLC, I-TAC, SDF-1α, and fractalkine), 2 growth factors (MMP-1, VEGF-α), and 5 soluble receptors (APRIL, CD40L, TWEAK, CD30 and TNFRII; were significantly differentially expressed between the two groups. ROC curves showed that only seven of them (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine, and Tweak) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, five cytokines: IFN-γ, IL-1 ß, IL-8, MIP-1ß, and TNF-α are positively associated with patients who developed resistance to taxol-platinum-based chemotherapy (CT). CONCLUSION: This study has revealed a first panel of 7 analytes (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine and Tweak) that can be used for early detection of EOC and a second panel of five cytokines (IFN-γ, IL-1ß, IL-8, MIP-1ß, TNF-α) that can help clinicians to identify EOC patients who are at higher risk to develop resistance to CT of EOC.

Intra-abdominal cystic lymphangioma in adults: A case series of 32 patients and literature review.

Introduction: Cystic lymphangioma (CL) is a benign tumor originating from the lymph vessels. Lymphangiomas in the abdominal cavity are extremely rare, particularly in adults.This article was designed to study the epidemiological, diagnostic difficulties, and therapeutic principles of intra-abdominal cystic lymphangioma (ACL) in adults. Material and methods: We conducted a single-center, retrospective study of 32 adult patients with ACL admitted to surgical department "A" in "La Rabta Hospital" in Tunis, from January 1998 through December 2020. The demographic, clinical, biological, radiological characteristics, histopathologic, and therapeutic data were collected, as well as the surgical intervention used and the postoperative immediate and late complications. Results: Thirty-two adult patients with ACL were recruited, including 20 females and 12 males. The median age at treatment was 47 (range 14-80) years. The most prevalent sites were the retroperitoneum (25%), the mesentery (21.9%), and the paracolic gutters (n = 18. 7%). Twenty patients underwent open surgery (62.5%), whereas 12 cases (37.5%) had laparoscopic surgery. Twenty-eight patients received total cystectomy (87%). Three recurrences were observed during follow-up (9.4%). Conclusion: The clinical features of CL in adults remain unclear. The diagnosis is only confirmed by histopathological examination after complete surgical resection. The laparoscopic approach is considered safe and feasible.

Clinico-Epidemiological Profile, Prognostic Factors and Treatment Outcome of Refractory Hodgkin Lymphoma.

Approximately 5-10% of patients with Hodgkin lymphoma are refractory to initial treatment. The aim of our study was to assess the clinico-epidemiological profile, prognostic factors and treatment outcome. A retrospective study was conducted over a period of 12 years between June 2006 and January 2018 at the oncology department of Salah Azaïz Institute. Thirty-one patients were included. The median age was 27 years with a female predominance (sex ratio = 0.93).The majority had an advanced stage (61%). IGEV regimen was the most commonly used salvage chemotherapy (n = 14). Age above 30 years was predictive of treatment failure after salvage therapy (p = 0.003). IGEV regimen showed better results than ICE protocol in terms of response to salvage therapy (p = 0.048). Seven patients had salvage radiotherapy. Four patients had autologous stem cell transplant. Progressive disease (n = 12) was the main cause of non-eligibility of autologous stem cell tansplant. Overall survival and progression free survival at 3 years were 50% and 5% respectively. The prognostic factors influencing the overall survival were age above 30 years (p = 0.001), advanced Ann Arbor stage before progression (p = 0.02), advanced Ann Arbor stage of refractory Hodgkin lymphoma (p = 0.001), histological subtype (p = 0.001), CD20 expression (p = 0.027) and non-response to salvage therapy (p = 0.004). The prognostic factor influencing progression free survival was the non-response to salvage therapy (p = 0.045). The prognosis of refractory Hodgkin lymphoma remains poor. The current standard secondary treatment consists of combination therapy, usually followed by autologous stem cell transplantat. Innovative therapies are needed to improve the prognosis of refractory Hodgkin lymphoma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01463-4.

Current Opinion and Practice on Peritoneal Carcinomatosis Management: The North African Perspective.

Background: The status of peritoneal surface malignancy (PSM) management in North Africa is undetermined. The aim of this study was to assess and compare current practice and knowledge regarding PSM and examine satisfaction with available treatment options and need for alternative therapies in North Africa. Methods: This is a qualitative study involving specialists participating in PSM management in North Africa. The survey analyzed demographic characteristics and current knowledge and opinions regarding PSM management in different institutions. We also looked at goals and priorities, satisfaction with treatment modalities and heated intraperitoneal chemotherapy (HIPEC) usefulness according to specialty, country, years of experience, and activity sector. Results: One-hundred and three participants responded to the survey (response rate of 57%), including oncologists and surgeons. 59.2% of respondents had more than 10 years experience and 45.6% treated 20-50 PSM cases annually. Participants satisfaction with PSM treatment modalities was mild for gastric cancer (3/10 [IQR 2-3]) and moderate for colorectal (5/10 [IQR 3-5]), ovarian (5/10 [IQR 3-5]), and pseudomyxoma peritonei (5/10 [IQR 3-5]) type of malignancies. Good quality of life and symptom relief were rated as main priorities for treatment and the need for new treatment modalities was rated 9/10 [IQR 8-9]. The perceived usefulness of systemic chemotherapy in first intention was described as high by 42.7 and 39.8% of respondents for PSM of colorectal and gastric origins, while HIPEC was described as highly useful for ovarian (49.5%) and PMP (73.8) malignancies. Conclusions: The management of PSM in the North African region has distinct differences in knowledge, treatments availability and priorities. Disparities are also noted according to specialty, country, years of expertise, and activity sector. The creation of referral structures and PSM networks could be a step forward to standardized PSM management in the region.

Skin toxicity after Filgrastim treatment for an Ewing's sarcoma patient.

INTRODUCTION: Filgrastim is a granulocyte colony-stimulating factor (GSCF) used in some chemotherapy regimen to prevent febrile neutropenia. Most common reaction of filgrastim are aches and pain including headaches, nausea and skin rash. CASE REPORT: We report the case of a patient who developed unusual, non-commonly reported adverse toxidermy to filgrastim. At first the eruption was limited to the lower members and genetics organs. Then it slowly spread across the whole body presenting as a polymorphic exanthematous-pustulosis lesions. MANAGEMENT & OUTCOME: A cutaneous biopsy was done, identifying a toxidermy modified by systemic treatment. A pharmacological study linked the role of filgrastim to these lesions. After switching from filgrastim to lénograstim, his lesions are completely gone and haven't flared up again. Thus, clearly imputing the use of filgrastim. DISCUSSION: The cutaneous reaction that has reported with use of GSCF are sweet syndrome, erythema nodosum, pyoderma nodosum and pyoderma gangrenosum. As far as we know, no acute generalized exanthematous pustulosis due to GSCF has been reported.

Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort.

BACKGOUND: Bladder cancer (BCa) is a heterogeneous disease caused by the interaction between environmental and genetic risk factors. The goal of this case-control study was to evaluate the implication of a selected SNP panel in the risk of BCa development in a Tunisian cohort. We were also interested in studying the interaction between this predictive panel and environmental risk factors. METHODS: The case/control cohort was composed with 249 BCa cases and 255 controls. The designed Bladder cancer hereditary panel (BCHP) was composed of 139 selected variants. These variants were genotyped by an amplification-based targeted Next-Generation Sequencing (NGS) on the Ion Torrent Proton sequencer (Life Technologies, Ion Torrent technology). RESULTS: We have found that rs162555, rs2228000, rs10936599, rs710521, rs3752645, rs804276, rs4639, rs4881400 and rs288980 were significantly associated with decreased risk of bladder cancer. However the homozygous genotypes for VPS37C (rs7104333, A/A), MPG (rs1013358, C/C) genes or the heterozygous genotype for ARNT gene (rs1889740, rs2228099, rs2256355, rs2864873), GSTA4 (rs17614751) and APOBR/IL27 (rs17855750) were significantly associated with increased risk of bladder cancer development compared to reference group (OR 2.53, 2.34, 1.99, 2.00, 2.00, 1.47, 1.96 and 2.27 respectively). We have also found that non-smokers patients harboring heterozygous genotypes for ARNT/rs2864873 (A > G), ARNT/ rs1889740 (C > T) or GSTA4/rs17614751 (G-A) were respectively at 2.775, 3.069 and 6.608-fold increased risk of Bca development compared to non-smokers controls with wild genotypes. Moreover the ARNT CT (rs1889740), ARNT CG (rs2228099), ARNT TC (rs2864873) and GSS GA genotypes were associated with an increased risk of BCa even in absence of professional risk factors. Finally the decision-tree analysis produced a three major BCa classes. These three classes were essentially characterized by an intensity of tobacco use more than 20 pack years (PY) and the CYP1A2 (rs762551) genotype. CONCLUSIONS: The determined association between environmental factors, genetic variations and the risk of Bca development may provide additional information to urologists that may help them for clinical assessment and treatment decisions. Nevertheless, the underlying mechanisms through which these genes or SNPs affect the clinical behavior of BCas require further studies.

Polymorphisms in NQO1 and MPO genes and risk for bladder cancer in Tunisian population.

BACKGROUND: NAD (P) H: quinone oxidoreductase (1) (NQO1-HGNC: 2874) and myeloperoxidase (MPO-HGNC: 7218) are two enzymes involved in phase II of the xenobiotic metabolism pathway. METHODS: In this study, a case-control analysis was conducted to investigate the relationship between genetic variations in the NQO1 (C609T, rs1800566; IVS1-27 C >G, rs689452) and MPO (G463A, rs2333227) genes and the risk for bladder cancer among Tunisian population. RESULTS: We have found that the MPO 463GA genotype was associated with a decreased risk of developing bladder cancer (p = 0.049; OR = 0.696; 95% CI 0.484-0.999). In contrast, we have found that the NQO1 609CT genotype could increase the risk of bladder cancer patients (p = 0.0039; OR = 1.454; 95% CI = 1.017-2.078). Moreover, patients with "NQO1 609 CT/IVS1-27 CG" genotype show a 2.180-fold increasing risk for developing bladder cancer in comparison to the control group with wild genotype. This OR is estimated at 5.6-fold in smokers patients with "NQO1 609 CT/IVS1-27 CG" genotype. Lastly, study findings suggest that the NQO1 IVS-27 *CG genotype (rs689452) is associated with a risk of progression to muscle invasive bladder cancer. CONCLUSION: Our study suggests that environmental risk factors in association to NQO1 genotypes (NQO1 609 CT/IVS1-27 CG) play an important role in the development of bladder cancer in Tunisian population.

Consensus on the Treatment and Follow-Up for the Nonmetastatic Castration-Resistant Prostate Cancer: A Report From the First Prostate Cancer Consensus Conference for Developing Countries.

PURPOSE: To present a summary of the recommendations for the treatment and follow-up for the biochemical recurrence of castration-resistant prostate cancer (PCa) as acquired through a questionnaire administered at the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 27 questions were identified as relating to this topic. Responses from the clinician were tallied and are presented in percentage format. Topics included the use of imaging in staging, treatment recommendations across different patient scenarios of life expectancy and prostate-specific antigen (PSA) doubling time, and follow-up for nonmetastatic castration-resistant PCa. RESULTS: A consensus agreed that in optimal conditions, positron emission tomography-computed tomography with prostate-specific membrane antigen would be used although in limited resource situations the combined use of CT of the abdomen and pelvic (or pelvic MRI), a bone scan, and a CT of the thorax or chest x-ray was recommended. In cases when PSA levels double in < 10 months, more than 90% of clinicians agreed on the use of apalutamide or enzalutamide, regardless of life expectancy. With a doubling time of more than 10 months, > 54% of experts recommended no treatment independent of life expectancy. More than half of the experts, regardless of resources, recommended follow-up with a physical examination and PSA levels every 3-6 months and imaging only in the case of symptoms. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support management for biochemical recurrence of castration-resistant PCa in areas of limited resources. Individual clinical decision making should be supported by available data.

Consensus for Treatment of Metastatic Castration-Sensitive Prostate Cancer: Report From the First Global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: International guideline recommendations may not always be extrapolated to developing countries where access to resources is limited. In metastatic castration-sensitive prostate cancer (mCSPC), there have been successful drug and imaging advancements that were addressed in the Prostate Cancer Consensus Conference for Developing Countries for best-practice and limited-resource scenarios. METHODS: A total of 24 out of 300 questions addressed staging, treatment, and follow-up for patients with mCSPC both in best-practice settings and resource-limited settings. Responses were compiled and presented in percentage of clinicians supporting each response. Questions had 4-8 options for response. RESULTS: Recommendations for staging in mCSPC were split but there was consensus that chest x-ray, abdominal and pelvic computed tomography, and bone scan should be used where resources are limited. In both de novo and relapsed low-volume mCSPC, orchiectomy alone in limited resources was favored and in relapsed high-volume disease, androgen deprivation therapy plus docetaxel in limited resources and androgen deprivation therapy plus abiraterone in high-resource settings were consensus. A 3-weekly regimen of docetaxel was consensus among voters. When using abiraterone, a regimen of 1,000 mg plus prednisone 5 mg/d is optimal, but in limited-resource settings, half the panel agreed that abiraterone 250 mg with fatty foods plus prednisone 5 mg/d is acceptable. The panel recommended against the use of osteoclast-targeted therapy to prevent osseous complications. There was consensus that monitoring of patients undergoing systemic treatment should only be conducted in case of prostate-specific antigen elevation or progression-suggestive symptoms. CONCLUSION: The treatment recommendations for most topics addressed differed between the best-practice setting and resource-limited setting, accentuating the need for high-quality evidence that contemplates the effect of limited resources on the management of mCSPC.

Pancreatic Metastasis of Renal Cell Carcinoma: A Surgical Indication for a Disseminated Disease.

Pancreatic metastasis (PM) of renal cancer is a rare condition. It is characterized by a long period after initial nephrectomy and a favorable prognosis compared to other pancreatic malignancies. Its diagnosis may confuse clinicians if the medical history is not known. In the era of targeted therapies for metastatic renal carcinoma, surgery stands as the best treatment option for PM of renal cancer. We report the case of a woman who underwent successfully left splenopancreatectomy for corporeal PM of renal cancer treated seven years ago. This case underlines the necessity of long-term follow-up of patients treated for kidney cancer.

Evaluation of ovarian reserve before and after chemotherapy.

BACKGROUND: Progress in oncology has improved patient survival. However, cancer chemotherapy can be gonadotoxic and affect their fertility. Recourse to fertility preservation before starting these treatments is therefore necessary in order to allow a better life quality after survival. The aim of this work was to study the impact of chemotherapy on ovarian reserve by AMH measurement. METHODS: This is a descriptive and longitudinal study from 2015 to 2018 carried out at Aziza Othmana hospital ART center in Tunis on patient aged less than 41 years who were candidates for fertility preservation. Patients included had AMH measurement prior to cancer treatment. We called them back to follow up the AMH level after chemotherapy. The AMH assay was performed by electrochemilumiescence technique. At the end, only 66 patients met the inclusion criteria. RESULTS: The most frequent pathologies were Hodgkin's lymphoma and breast cancer. The mean age of patients was 26.7 ± 6.8. The most used chemotherapy protocols were BEACOPP, ABVD or the combination of both in lymphoma and FEC + TXT for breast cancer treatment. A significant difference between AMH before and after chemotherapy was found for BEACOPP and FEC + TXT protocols (p < 10 3). The patient's age was correlated with the AMH decrease after chemotherapy (r = 0.577, p < 10 3). CONCLUSION: Our results showed that the high risk gonadotoxicity protocols were BEACOPP for lymphoma treatment and FEC + TXT for breast cancer treatment. However, studies with a larger sample and more time extended monitoring are necessary for a better gonadotoxicity understanding of the cancer treatments available today.

Prognostic factors in High-Grade Localized Osteosarcoma of the Extremities: The Tunisian Experience.

BACKGROUND: Osteosarcoma is the most frequent bone cancer occurring in children and adolescents aged 10-20 years. Several prognostic factors have been identified by studies done at western centers. The aim of our study was to identify the prognostic factors in Tunisian patients in order to improve their management. METHODS: We reviewed the data of localized limb osteosarcoma patients treated in Salah Azaïz Institute from January 1980 to December 2018. Patient's treatment and survival variables were assessed. Patients received a neoadjuvant chemotherapy and underwent surgery in an expert center. They received afterward an adjuvant chemotherapy depending on the tumor necrosis assessed by Huvos. RESULTS: Eighty-five patients were enrolled. Mean duration of follow-up was 30 months (range 1-297 months). Males were 1.6 times more frequent, median age was 17 (from 1 to 62 years). Conventional osteoblastic osteosarcoma was the most frequent histological subtype (77%). Median tumor size was 10 cm. Femoral location was the most frequent (60%). The overall average history of symptoms was 103 days (4 to 423 days). The 5-year overall-survival was 38% and the event free survival 32%. Tumor site, lactate dehydrogenase levels, high methotrexate levels at 24 h, clinical evaluation of the tumor perimeter, surgery type and delay of relapse were found to affect overall survival. Tumor site, Lactate dehydrogenase levels and clinical evaluation of the tumor perimeter affected the progression free survival. CONCLUSION: Demographic characteristics of Tunisian patients are mainly the same than worldwide. Femoral site, normal level of lactate dehydrogenase, a clinical response during neoadjuvant treatment, an R0 surgery, a delay of relapse over 2 years and Median H24 Methotrexate level superior to 4.4 µmol/l were associated with a better prognosis in our study.

Uncovering the expression patterns and the clinical significance of miR-182, miR-205, miR-27a and miR-369 in patients with urinary bladder cancer.

BACKGROUND: Given the high recurrence and progression rates and the absence of reliable markers for early detection and prognosis prediction of patients with urothelial bladder cancer (BCa), the exploration of new biomarkers with high specificity is imperative. Mainly, microRNAs (miRNAs), which are involved in the initiation and the progression of BCa. Herein, the expression patterns of miR-182, miR-205, miR-27a and miR-369 were evaluated in patients with urothelial BCa. METHODS AND RESULTS: The expression levels of the miRNAs were investigated in 90 FFPE tissue samples (23 LG NMIBC, 44 HG NMIBC, 23 MIBC) and 10 non tumoral bladder tissues using TaqMan based RT-qPCR. Data analysis was performed using 2-ΔΔCT method. Correlation to clinical characteristics of the patients was performed using descriptive statistics and the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of all miRNAs. MiR-27a, miR-205 and miR-369 were down-regulated whereas miR-182 was up-regulated in patients compared to controls (p < 0.001). MiR-205 and miR-182 positively segregate between NMIBC and MIBC (p = 0.002 and p = 0.000 respectively) whereas the distribution of miR-27a's expression among these tumor groups was almost significant (p = 0.05) and that of miR-369's expression was irrelevant (p = 0.618). Interestingly, miR-182 was discriminative between LG NMIBC and HG NMIBC (p < 0.001) and Ta/T1 tumors (p = 0.000). Furthermore, high levels of miR-182 were potentially predictive of progression in NMIBC patients (p = 0.01). CONCLUSION: Collectively, a selection of miRNAs was found to be aberrantly expressed in BCa suggesting a potential diagnostic value in BCa. In addition, the clinical value of miR-182 and miR-205 as potential prognosis biomarkers was highlighted. Indeed, our data provide additional insights into cancer biology. Further functional or target studies are mandatory to strengthen these findings.