Optimization of high-dose methotrexate prophylaxis for central nervous system relapse in diffuse large B-cell lymphoma: a multicenter analysis.

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare but devastating event. Intravenous high-dose methotrexate (HD-MTX) is recommended as CNS prophylaxis, but the optimal timing and dose has not been elucidated. Here, we report a multicenter analysis of prophylactic HD-MTX administration for DLBCL. Two hundred eighty-four patients receiving HD-MTX either concurrent with each induction chemotherapy cycle (n = 221) or at the end of induction therapy (EOI, n = 63) were included. Patients with CNS-IPI scoring 4-6, and/or testicular involvement, and/or double/triple hit lymphoma, were stratified into the high-risk group and the others into the moderate-risk group. Concurrent HD-MTX was associated with increased risk of grade 3/4 treatment-related toxicity (OR,1.49; P = 0.006) and subsequent chemotherapy delays (OR, 1.87; P = 0.003) in multivariate analysis. With a median follow-up of 36.0 months, no significant difference in CNS relapse rate was identified between the concurrent and EOI groups (3.2% vs 4.8%, P = 0.34), even in the high-risk group. Analysis on systemic MTX dose suggested that high-dose MTX (≥ 2 g/m2) was associated with better CNS relapse control only in the high-risk group, but not in the moderate-risk group. This study may elucidate the superiority of EOI HD-MTX to some extent. High MTX dose (≥ 2 g/m2) may not be necessary for the moderate-risk patients.

CaboPoint: a phase II study of cabozantinib as second-line treatment in patients with metastatic renal cell carcinoma.

Cabozantinib is an inhibitor of multiple tyrosine kinases, including AXL, MET and VEGF receptors. Here, we describe the rationale and design for the phase II CaboPoint trial (ClinicalTrials.gov identifier: NCT03945773), which will evaluate the efficacy and safety of cabozantinib as a second-line treatment in patients with unresectable, locally advanced or metastatic renal cell carcinoma whose disease has progressed despite checkpoint inhibitor therapy. Patients will be recruited into two cohorts: prior ipilimumab plus nivolumab (cohort A) or prior checkpoint inhibitor-VEGF-targeted therapy (cohort B). All patients will receive once-daily oral cabozantinib 60 mg for up to 18 months. The primary end point is objective response rate. Secondary end points include overall survival, progression-free survival and safety.

Most patients diagnosed with kidney cancer have a type of tumor called renal cell carcinoma (RCC). Most cases of RCC are described as 'clear cell' because the tumor cells appear clear when viewed under a microscope. Cabozantinib is an oral treatment approved for use in some patients with advanced RCC, including those with clear cell disease. Cabozantinib slows RCC progression by targeting pathways that help tumors grow, including inhibition of VEGF. The ongoing CaboPoint study will assess the efficacy and safety of cabozantinib in patients with clear cell RCC that has progressed despite previous anticancer treatment involving an immune checkpoint inhibitor (CPI). CPI therapy helps the body to detect tumors and to launch its own anticancer response. Patients included in CaboPoint must be adults with clear cell RCC that is not suitable for surgery and has either spread within the kidney or to other organs, despite previous CPI-based therapy. In total, 250 patients will be recruited: 125 who received previous combination CPI treatment (ipilimumab plus nivolumab; group A) and 125 who received previous CPI treatment plus anti-VEGF therapy (group B). Patients will start cabozantinib at a dose of 60 mg/day and continue treatment for up to 18 months. The main outcome to be studied will be the number of patients with a reduction in tumor size (objective response rate). The length of time patients live with their disease, the effect of treatment on symptoms and patient safety will also be evaluated. Clinical trial registration: NCT03945773 (ClinicalTrials.gov).

MAGEA10 expression is a predictive marker of early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer.

BACKGROUND: Resection for hepatic recurrence after gastrectomy in patients with gastric cancer may be curative; however, the prediction of hepatic recurrence remains intractable. Therefore, we aimed to explore predictive markers for hepatic recurrence in gastric and gastroesophageal junction cancer based on genetic information. METHODS: This study recruited 154 patients who underwent curative gastrectomy for pathological stage II or III primary gastric and gastroesophageal junction adenocarcinoma. Genes associated with hepatic recurrence were comprehensively analyzed using whole-exome sequencing and gene expression profiling (GEP), followed by immunohistochemistry analysis for MAGEA10. The cumulative incidences of hepatic recurrence, relapse-free survival, and overall survival were evaluated. RESULTS: A total of 12 patients with early hepatic recurrences were found within 2 years of surgery. Although there were no distinct gene mutations in recurrent patients, upregulation of MAGEA10 was identified in patients with early hepatic recurrence using GEP analysis. Immunostaining for MAGEA10 stained the cell nuclei in 29 (18.8%) of 154 samples. Furthermore, protein expression of MAGEA10 on immunohistochemistry was significantly related to a high MAGEA10 mRNA expression, high cumulative incidences of hepatic recurrence, and poor relapse-free survival. Overall survival did not differ significantly between positive and negative immunohistochemical staining for MAGEA10. The sensitivity and specificity of MAGEA10 staining for early hepatic recurrence were 58.3% and 84.5%, respectively. CONCLUSIONS: MAGEA10 represents a promising predictive marker for early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer.

A case of endocrine mucin-producing sweat gland carcinoma with distant metastasis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.

Cutaneous adnexal carcinosarcoma: Immunohistochemical and molecular evidence of epithelial mesenchymal transition.

Cutaneous carcinosarcomas are rare biphenotypic tumors that simultaneously show epithelial and mesenchymal differentiation. The most common carcinomatous components in skin carcinosarcomas are basal cell carcinoma and squamous cell carcinoma; adnexal carcinomas are rarely encountered. We report a case of an adnexal carcinoma with ductal and squamous differentiation and spindle cell component, which is interpreted as carcinosarcoma. Loss of immunohistochemical expression of E-cadherin and ß-catenin detected in the sarcomatous component suggested epithelial mesenchymal transition (EMT). RNA sequencing analysis identified several gene mutations and alterations such as translocations and upregulations/downregulations, either shared by the two components of the tumor or differentially present in the carcinoma or the sarcoma parts. Thus, mutations in genes, such as TP53, were found in both components of the tumor while mutations in PDGFRA and RB1 (a pathogenic missense mutation) were exclusively present in the sarcomatous areas, further supporting EMT. EMT is a dynamic process by which tumors acquire mesenchymal phenotype while simultaneously losing epithelial properties. Although the pathways involved in EMT have been extensively studied, this phenomenon still needs to be investigated in cutaneous tumors of adnexal origin for a better understanding of their pathogenesis. These molecular changes may represent promising targets for personalized therapies.

Pulmonary recurrence after radical hysterectomy for uterine cervical carcinoma.

Pulmonary spread from carcinoma of the uterine cervix, though uncommon, has been reported in 2.2-9.1% of all cervical cancers. The aim of this study was to evaluate the surgical, clinical, pathological factors and clinical outcomes of cervical cancer patients with pulmonary recurrence (PR).This study included 17 cervical cancer patients with PR after radical hysterectomy. The entire cohort consisted of 413 patients whose surgeries (type III radical hysterectomy + pelvic ± para-aortic lymphadenectomy) had been performed in our Gynaecologic Oncology Clinic between 1993 and 2018. Tumour size, lymph node metastasis and receiving adjuvant therapy were found to be effective for PR on univariate analyses in the main cohort (p = .042, p < .001 and p = .001, respectively). Therefore, performing adjuvant therapy to reduce the PR must be assessed properly with the information of lymph node status and tumour size obtained from the final pathology reports.Impact StatementWhat is already known on this subject? Pulmonary spread from carcinoma of the uterine cervix has been reported in 2.2-9.1% of all cervical cancers. Data related to clinico-pathological features of patients with pulmonary recurrence (PR) is limited. Diagnosis of a PR is considered to worsen the prognosis.What do the results of this study add? Tumour size, lymph node metastasis and receiving adjuvant therapy were found to be effective for PR on univariate analyses.What are the implications of these findings for clinical practice and/or further research? Performing adjuvant therapy to reduce the PR must be assessed properly with the information of lymph node status and tumour size obtained from the final pathology reports in patients with uterine cervical carcinoma.

Repeat stereotactic radiosurgery for the management of locally recurrent brain metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is a well-established treatment option for brain metastases (BM). Repeat SRS for progressive BM is an increasingly used paradigm, although little data is available to support this practice. The goal of this study was to assess the safety and efficacy of a second SRS procedure on a previously treated BM. METHODS: We performed a retrospective metastasis-level analysis of patients who underwent two SRS procedures on the same lesion and for whom at least 6 months of radiological follow-up was available. The data collected included patient characteristics, clinical symptoms at time of treatment, SRS parameters, radiological response per RANO-BM criteria, clinical evolution and survival. RESULTS: Seventy-five BM in 56 patients were included in the analysis. Most frequent primary histologies were non-small-cell lung cancer (59%) and breast cancer (19%). At the second SRS, median treatment volume was 1.19 cc (range 0.07-20.6) treated with a median margin dose of 18 Gy (range 12-20) at the 50% isodose line (range 30-80%). Median follow-up was 11 months. Progression per RANO-BM criteria occurred in 31%, yielding actuarial local control at 1, 2, and 5 years of 68%, 54% and 54% respectively. At last follow-up, 10 patients (18%) had improved relative to the initial presentation, while 21 (38%) were stable and 25 (44%) were deteriorated. Radiation-induced edema and radionecrosis occurred in 8.3% and 5% respectively. The median survival from the diagnosis of BM was 30 months. CONCLUSION: Repeat SRS is a safe and effective novel therapeutic approach to consider in carefully selected patients.

Canine myxosarcomas, a retrospective analysis of 32 dogs (2003-2018).

BACKGROUND: Myxosarcomas are known to be classified as soft tissue sarcomas. However, there is limited clinical characterization pertaining specifically to canine cutaneous myxosarcomas in the literature. The objective of this study is to evaluate the local recurrence rate, metastatic rate and prognosis of canine myxosarcoma. RESULTS: A total of 32 dogs diagnosed with myxosarcoma via histopathology were included in this retrospective study. All dogs had surgical resection. No adjunct treatments were performed in 9 dogs, while 22 dogs also received either radiation therapy or chemotherapy, or a combination of both. One dog received only NSAID after surgery. Overall median survival time (MST) was 730 days (range 20-2345 days). The MST of dogs with a tumor mitotic count < 10/10 HPF was 1393 days (range 20-2345 days). The dogs with a tumor mitotic count of 10 or greater/10 HPF had a MST of 433 days (range 169-831 days). There was no significant difference of MST among different treatment modalities. Local recurrence was noted in 13 cases (40.6%) and the median time to recurrence was 115.5 days (range 50-1610 days). The median time to local recurrence in dogs with mitotic count of < 10/10 HPF was 339 days (range 68-1610 days) and in dogs with mitotic count of 10 or greater/10 HPF was 119 days (range 50-378). Metastasis to local lymph node or lung was noted in 8 cases (25%) with median time to metastasis of 158.5 days (range 0-643 days). CONCLUSIONS: Based on the results of this retrospective study, myxosarcoma may have a higher local recurrence rate and risk of metastasis to the local lymph nodes compared to other soft tissue sarcomas.

Outcomes after a first and/or second salvage treatment in patients with oligometastatic prostate cancer recurrence detected by (18-F) choline PET-CT.

OBJECTIVE: The primary objective of this study was to assess clinical outcomes in patients with oligometastatic prostate cancer recurrence after single or repeated salvage radiation treatment. METHODS: Forty-nine consecutive prostate cancer patients diagnosed with oligometastatic recurrence on Ch-PET have been prospectively treated. Seven (23%) patients had castrate-resistant disease. Clinical outcomes were assessed using the Kaplan-Meier method. Potential prognostic factors were examined using univariate proportional hazards regression. RESULTS: The treatments administered to the initial oligorecurrence sites were intensity-modulated radiotherapy (IMRT) ± ADT (26 patients; 53%) and stereotactic ablative radiotherapy (SABR) ± ADT (23 patients; 47%). With a median follow-up of 24 months (range 6-39), 24 patients developed a biochemical failure. Twenty out of the 24 relapsed patients underwent a second Ch-PET/CT. Seven patients presented poly-metastatic relapse and 10 oligometastatic diseases. Six of 10 patients with a second oligorecurrence were treated again with SABR. Overall, 102 lesions were treated. Local control was detected in 45 (91.8%) patients. No relevant (grade ≥ 2) toxicity was reported, and there was no grade 3 toxicity. On univariate analysis, none of the variables were significantly predicted for clinical disease-free survival. At last follow-up visit, 24 patients (40%) were free from biochemical failure and 37 (71%) patients were free from clinical disease. The 2-year OS and PCSS were 91.8% and 95.9% respectively. CONCLUSION: Salvage IMRT or SBRT of oligometastatic prostate cancer recurrence is associated with a prolonged cDFS. This may result in a longer time to develop castrate-resistant disease and a longer time without systemic therapies.

Repeat hepatectomy with systemic chemotherapy might improve survival of recurrent liver metastasis from colorectal cancer-a retrospective observational study.

BACKGROUND: Although hepatectomy for metastatic colorectal cancer (mCRC) prolongs survival in up to 40% of people, recurrence rates approach 70%. We used a multidisciplinary approach to treat recurrent liver metastases, including chemotherapy, surgery, and palliative care. On the other hand, development of chemotherapeutic agents is remarkable and improves long-term survival. However, whether chemotherapy and repeat hepatectomy combination therapy improve survival or not is still unclear. The aim of this study was to analyze the outcomes of repeat hepatectomy with systemic chemotherapy for mCRC. METHODS: Following Institutional Review Board approval, we reviewed the records of all patients who underwent hepatectomy for mCRC between 1974 and 2015 at Fujita Health University Hospital. We used the Kaplan-Meier method to estimate overall survival from the first and last hepatectomy in multi hepatectomy cases after 2005 and compared outcomes between groups using the log-rank test. RESULTS: A total of 426 liver resections were performed for mCRC; of these, 236 cases were performed after 2005 (late group). In 118 (50%) cases, the site of recurrence was the liver, 59 (50%) underwent repeat hepatectomy, and 14 cases had ≥ 2 repeat hepatectomies. Overall survival (OS) before and after 2005 was 42.2 and 64.1 months, respectively, with the late group having better OS compared to the early (1974-2004) group. OS for single hepatectomy cases was 83.2 months, for two hepatectomies was 42.9 months, and for three hepatectomies was 35.3 months. In total, 59 patients did not undergo surgery after recurrence with an OS of 28.7 months. Mortality of the second and third repeat hepatectomy was 1.7% and 15.3%, respectively. CONCLUSION: Repeat hepatectomy with systemic chemotherapy for mCRC is feasible and might achieve improved survival in carefully selected patients.

Recurrent Dermatofibrosarcoma Protuberans of the Parotid: A case report and review of literature.

In 1924, Darier and Ferrand described Dermatofibrosarcoma Protuberans as a progressive and recurring dermatofibroma. It is a locally aggressive sarcoma originating from dermal and subdermal tissue of the skin. It usually begins as a small plaque that grows over a period and later manifests as multiple small subcutaneous nodules. It is more commonly found in females as compared to males and typically occurs in between 2nd and 5th decades of life. Most frequently involved regions of the body are torso and proximal ends of extremities and very rarely head and neck region is the site of involvement. The mainstay of treatment of this entity is surgery. The rate of recurrence of this disease is very high in about 50% of the cases and it may also express rare distant metastasis. It is a radiosensitive tumour and radiation may play a role in reducing risk of recurrence. We present a case of a 35 years old male with recurrent Dermatofibrosarcoma Protuberans of right parotid gland.

Outcomes of Surgical and Chemotherapeutic Treatments of Goblet Cell Carcinoid Tumors of the Appendix.

BACKGROUND: Goblet cell carcinoids (GCCs) of the appendix are rare mucinous neoplasms, for which optimal therapy is poorly described. We examined prognostic clinical and treatment factors in a population-based cohort. METHODS: Patients diagnosed with GCC from 1984 to 2014 were identified from the British Columbia Cancer Agency and the Vancouver Lower Mainland Pathology Archive. RESULTS: Of 88 cases with confirmed appendiceal GCCs, clinical data were available in 86 cases (annual population incidence: 0.66/1,000,000). Median age was 54 years (range 25-91) and 42 patients (49%) were male. Metastasis at presentation was the strongest predictor of overall survival (OS), with median OS not reached for stage I-III patients, and measuring 16.2 months [95% confidence interval (CI) 9.1-29] for stage IV patients. In 67 stage I-III patients, 51 (76%) underwent completion hemicolectomy and 9 (17%) received adjuvant 5-fluorouracil-based chemotherapy. No appendicitis at initial presentation and Tang B histology were the only prognostic factors, with inferior 5-year recurrence-free survival (53 vs. 83% with appendicitis, p = 0.02; 45% Tang B vs. 89% Tang A, p < 0.01). Of 19 stage IV patients, 10 (62.5%) received 5-fluorouracil-based chemotherapy and 11 (61%) underwent multiorgan resection (MOR) ± hyperthermic intraperitoneal chemotherapy (HIPEC). Low mitotic rate and MOR ± HIPEC were associated with improved 2-year OS, but only MOR ± HIPEC remained significant on multivariate analysis (hazard ratio 5.4, 95% CI 1.4-20.9; p = 0.015). CONCLUSIONS: In this population-based cohort, we demonstrate excellent survival outcomes in stage I-III appendiceal GCCs and clinical appendicitis. Hemicolectomy remains the standard treatment. In metastatic disease, outcomes remain poor, although MOR ± HIPEC may improve survival.

Multicentre study of laparoscopic or open assessment of the peritoneal cancer index (BIG-RENAPE).

BACKGROUND: The peritoneal cancer index (PCI) is a comparative prognostic factor for colorectal peritoneal metastasis (CRPM). The ability of laparoscopy to determine the PCI in consideration of cytoreductive surgery remains undetermined, and this study was designed to compare it with laparotomy. METHODS: A prospective multicentre study was conducted for patients with no known CRPM, but at risk of peritoneal disease. Surgery began with laparoscopic exploration followed by open exploration to determine the PCI. Concordance between laparoscopic and open assessment was evaluated for the diagnosis of CRPM and for the PCI. RESULTS: Among 50 patients evaluated, CRPM recurrence was found in 29 (58 per cent) and 34 (68 per cent) at laparoscopic and open surgery respectively. Laparoscopy was feasible in 88 per cent (44 of 50) and deemed satisfactory by the surgeon in 52 per cent (26 of 50). Among the 25 evaluable patients with satisfactory laparoscopy, there was concordance of 96 per cent (24 of 25 patients) and 38 per cent (10 of 25) for laparoscopic and open assessment of CRPM and the PCI respectively. Where there were discrepancies, it was laparoscopy that underestimated the PCI. CONCLUSION: Laparoscopy may underestimate the extent of CRPM.

Treatment Outcomes and Prognostic Factors After Recurrence of Esophageal Squamous Cell carcinoma.

BACKGROUND: The evaluation of treatment outcomes and detection of prognostic factors after recurrence are very important for tailoring optimal therapies for individual patients with recurrent esophageal cancer. METHODS: We reviewed 133 patients in whom esophageal squamous cell carcinoma (ESCC) recurred after curative surgery, and assessed recurrence patterns, treatment outcomes and prognostic factors. RESULTS: Recurrence in 57 (42.9%), 54 (40.6%) and 22 (16.5%) patients was locoregional, distant and combined, respectively. The median amounts of elapsed time until recurrence and median survival after recurrence for all patients were 9.1 and 8.3 months, respectively. Univariate and multivariate analyses selected time to recurrence (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.999; p = 0.04), recurrence location (locoregional vs. distant: HR, 1.63; 95% CI, 1.03-2.61; p = 0.04), number of organs with recurrence (1 vs. 3: HR, 3.49; 95% CI, 1.23-9.87; p = 0.02) and treatment after recurrence (best supportive care, [BSC] vs. chemotherapy [CT] or radiation therapy [RT]: HR, 0.37; 95% CI, 0.15-0.94; p = 0.04; BSC vs. CT and RT: HR, 0.50; 95% CI, 0.26-0.94; p = 0.03; BSC vs. surgery: HR, 0.47; 95% CI, 0.25-0.88; p = 0.02) as independent factors for survival after recurrence. Seventeen (12.8%) patients who had localized lymph node recurrence and lung oligometastasis and received multidisciplinary therapy after recurrence survived for >3 years thereafter. CONCLUSION: Despite the poor survival of patients with ESCC and early or distant recurrence or recurrence in ≥3 recurrent organs, appropriate multimodal therapies should be tailored for individual patients with recurrent ESCC.

Vismodegib and the Hedgehog Pathway Inhibitors: A Historical Perspective to Current Clinical Application.

Vismodegib (Erivedge, Genentech-Roche) is the first in class of Hedgehog pathway inhibitors approved for treatment of metastatic basal cell carcinoma (BCC), or locally advanced BCC that has recurred after surgery or is not amenable to surgery or radiation. Its path to discovery has been unique and traces its origin to corn lilies, sheep, Drosophila flies, and the Hedgehog signaling pathway. J Drugs Dermatol. 2018;17(5):506-508.

Isolated Urethral Metastasis From a Primary Ovarian Malignancy.

BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest of gynaecological cancers, often manifesting itself at a later stage (stage 3 and 4). Metastases and recurrences tend to be limited to the abdominopelvic cavity, and cutaneous metastases are rare. CASE SUMMARY: We report an interesting case of a 51-year-old who presented 2 years after her initial treatment with surgery and adjuvant chemotherapy for a stage IIB with an isolated recurrence in the external urethral meatus. CONCLUSION: This case highlights the need for clinicians and patients to remain vigilant during follow-up visits to rule out recurrences despite nonspecific symptoms reported by patients.

Use of diffusion-weighted MRI to modify radiosurgery planning in brain metastases may reduce local recurrence.

Stereotactic radiosurgery (SRS) is an effective and well tolerated treatment for selected brain metastases; however, local recurrence still occurs. We investigated the use of diffusion weighted MRI (DWI) as an adjunct for SRS treatment planning in brain metastases. Seventeen consecutive patients undergoing complete surgical resection of a solitary brain metastasis underwent image analysis retrospectively. SRS treatment plans were generated based on standard 3D post-contrast T1-weighted sequences at 1.5T and then separately using apparent diffusion coefficient (ADC) maps in a blinded fashion. Control scans immediately post operation confirmed complete tumour resection. Treatment plans were compared to one another and with volume of local recurrence at progression quantitatively and qualitatively by calculating the conformity index (CI), the overlapping volume as a proportion of the total combined volume, where 1 = identical plans and 0 = no conformation whatsoever. Gross tumour volumes (GTVs) using ADC and post-contrast T1-weighted sequences were quantitatively the same (related samples Wilcoxon signed rank test = -0.45, p = 0.653) but showed differing conformations (CI 0.53, p < 0.001). The diffusion treatment volume (DTV) obtained by combining the two target volumes was significantly greater than the treatment volume based on post contrast T1-weighted MRI alone, both quantitatively (median 13.65 vs. 9.52 cm3, related samples Wilcoxon signed rank test p < 0.001) and qualitatively (CI 0.74, p = 0.001). This DTV covered a greater volume of subsequent tumour recurrence than the standard plan (median 3.53 cm3 vs. 3.84 cm3, p = 0.002). ADC maps may be a useful tool in addition to the standard post-contrast T1-weighted sequence used for SRS planning.

CEACAM1 is associated with recurrence after hepatectomy for colorectal liver metastasis.

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is re-expressed at the invasion front of colorectal cancer. CEACAM1 expression at metastatic sites remains to be investigated. The current study aims to clarify the association between CEACAM1 expression and recurrence after hepatectomy of colorectal liver metastasis and to address whether CEACAM1 induces tumor-initiating properties needed for growth at metastatic sites. METHODS: Immunohistochemical analyses for CEACAM1 were performed in 67 patients with liver metastasis of colorectal cancer who had undergone curative hepatectomy. The risk factors for postoperative recurrence were calculated based on a CEACAM1 cytoplasmic domain isoform at the primary tumor invasion front. To investigate the effects of CEACAM1 cytoplasmic isoforms on HT29 and HCT116 colorectal cancer cells, Western blotting for CD44 and CD133, flow cytometry for ALDH1 activity, and soft-agar colony formation assay were performed. RESULTS: CEACAM1 long (CEACAM1-L) and short (CEACAM1-S) cytoplasmic domain isoforms are strongly expressed on cancer cells in the liver metastases. Enhanced CEACAM1-S expression in the state of CEACAM1-L dominance at the primary tumor invasion front was an independent factor for colorectal cancer recurrence after curative hepatectomy. CEACAM1-4S-transfected HT29 and HCT116 cells had significantly higher CD44 expression and ALDH1 activity and increased the growth in anchorage-independent condition. CONCLUSIONS: High expression of CEACAM1-S at the primary lesion invasion front is associated with recurrence and prognosis of patients with colorectal liver metastasis after curative hepatectomy. The expression of CEACAM1-4S enhances the tumor-initiating property of colorectal cancer cells.

Surgical treatment in non-small cell lung cancer with pulmonary oligometastasis.

BACKGROUND: Previous studies have demonstrated survival benefits for local treatment in solitary metastatic non-small cell lung cancer (NSCLC).This study aimed to investigate the effect of local surgery for NSCLC with pulmonary oligometastasis. METHODS: This study included 21 patients of NSCLC with pulmonary oligometastasis between January 2003 and December 2013, which were divided into two groups, group A (11 cases) for local surgery and group B (10 cases) for systematic chemotherapy, compared the median survival time (MST) and 5-year survival rate between the two groups, and analyzed the impact of the pathological types, the TNM and pN stage of primary tumor, the site, and the mode and number of oligometastatic nodule on group A. RESULTS: The MST of group A and B were 37 and 11.6 months respectively, 5-year survival rates were 18.2 and 9.1% respectively (p < 0.05). Patients with single nodule, oligo-recurrence, primary tumor of pN0, TNM stage I or II obtained higher survival rate than those with multiple nodules, sync-oligometastases, pN1-2, stage III or IV in group A (p < 0.05). There was no significant survival time difference among pathological types of primary tumor and oligometastatic site (p > 0.05). CONCLUSION: Local surgery significantly prolonged the overall survival time and 5-year survival rate of primary NSCLC with pulmonary oligometastasis.

Outcomes of patients with advanced stage ovarian cancer with intestinal metastasis.

OBJECTIVES: The aim of this study is to evaluate the results of advanced stage (stage IIIB-IVB) ovarian cancer (OC) patients with intestinal metastasis, and to investigate the factors that affect survival. MATERIAL AND METHODS: Patients who underwent cytoreductive surgery (CS) for FIGO stage IIIB-IVB OC with metastasis in the intestinal system, at Tepecik Research and Treatment Hospital between 2008-2014, were analyzed retrospectively. Patients with borderline ovarian tumor; those who had previously undergone radiation therapy and/or hysterectomy and patients having secondary or tertiary cytoreduction were excluded and 49 patients were included and analyzed in this study. Hysterectomy, bilateral salpingo-oopherectomy, pelvic and para-aortic lymph node sampling, resection of bulky lymph nodes and omentectomy were performed. Optimal cytoreduction was accepted as that which left residual tumor ≤ one cm maximum size. RESULTS: The risk factors affecting OS interval were investigated according to Cox' regression analysis. Optimality of the primary CS (P = 0.008 and HR = 5.202) and cancer stage (P = 0.016 and HR = 6.083) were found to be statistically significant factors. CONCLUSIONS: Achieving optimal CS is the most important aim for the general surgeon carrying out an intestinal resection procedure. Although resection procedures are superior in providing the desired optimal results when compared to excision surgery, their higher complication rates and subsequent lower quality of life must be taken into consideration when choosing either resection or excision methods; surgical intervention should always be kept to the minimum possible.