Prognostic Factors of Melanoma Patients with Satellite or In-Transit Metastasis at the Time of Stage III Diagnosis

Background

Prognosis of patients with loco-regional skin metastases has not been analyzed in detail and the presence or absence of concurrent lymph node metastasis represents the only established prognostic factor thus far. Most studies were limited to patients already presenting with skin lesions at the time of initial diagnosis. We aimed to analyze the impact of a broad penal of prognostic factors in patients with skin metastases at the time of first metastatic spread, including patients with synchronous lesions already present at the time of initial diagnosis, stage I/II patients with loco-regional recurrence and patients initially presenting with skin metastasis but unknown primary melanoma.

Patients and Methods

We investigated disease-specific survival of 380 patients treated at our department between 1996 and 2010 using Kaplan Meier survival probabilities and Cox-proportional hazard analysis.

Results

Five-year survival probability was 60.1% for patients with skin metastases only and 36.3% for those with synchronous nodal metastases. The number of involved nodes and a tumor thickness of at least 3 mm had independent negative impact on prognosis. A strong relationship was identified between the risk of death and the number of involved nodes. Neither ulceration nor the timing of the first occurrence of metastases as either in stage I/II patients, at the time of excision of the primary melanoma or initially in patients with unknown primary tumor, had additional effects on survival.

Conclusion

Lymph node involvement was confirmed as the most important prognostic factor for melanoma patients with loco-regional skin metastasis including those with unknown primary tumor and stage I/II patients with skin recurrence. Consideration of the tumor thickness and of the number of involved lymph nodes instead of the exclusive differentiation into presence vs. absence of nodal disease may allow a more accurate prediction of prognosis for patients with satellite or in-transit metastases.     

Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma

Background

Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination.

Methods

Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria.

Results

61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks).

Conclusions

Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.     

Primary mucosal sinonasal melanoma—Case report and review of the literature. The role of complex treatment-surgery and adjuvant radiotherapy

Aim

The place of adjuvant radiotherapy in the treatment of sinonasal melanoma.

Background

Sinonasal mucosal melanoma is a rare disease with poor prognosis and requires a complex treatment. Elective neck dissection in patients with N0 and adjuvant radiotherapy has been a source of controversy. High late regional recurrence rates rise questions about elective irradiation of the neck nodes in patients with N0 stage disease.

Methods

We present our two years’ follow up in a case of locally advanced sinonasal melanoma and literature review of the treatment options for mucosal melanoma.

Results

In locally advanced sinonasal melanoma treated with surgical resection, postoperative radiotherapy and chemotherapy we had local tumor control. Two years later, a regional contralateral recurrence without distant metastasis occurred.

Conclusions

Literature data for frequent neck lymph nodes recurrences justify elective neck dissection. Postoperative elective neck radiotherapy for patients with locally advanced sinonasal melanoma and clinically N0 appears to decrease the rate of late regional recurrences.     

Time-Varying Pattern of Postoperative Recurrence Risk of Early-Stage (T1a-T2bN0M0) Non-Small Cell Lung Cancer (NSCLC): Results of a Single-Center Study of 994 Chinese Patients

Background

The aim of this study was to analyze the time-varying pattern of recurrence risk of early-stage (T1a-T2bN0M0) non-small cell lung cancer (NSCLC) after surgery using the hazard function and identify patients who might benefit from adjuvant chemotherapy.

Patients and Methods

This retrospective study enrolled 994 patients with early-stage NSCLC who underwent radical surgical resection between January 1999 and October 2009. Survival curves were generated using the Kaplan-Meier method, and the annual recurrence hazard was estimated using the hazard function.

Results

The median recurrence-free survival (RFS) was 8.8 years. The life table survival analysis showed that the 1-year, 3-year, 5-year and 10-year recurrence rates were 82.0%, 67.0%, 59.0% and 48.0%, respectively. Approximately 256 (25.7%) patients experienced relapse [locoregional: 32 (3.2%) and distant: 224 (22.5%)], and 162 patients died from cancer. The annual recurrence hazard curve for the entire population showed that the first major recurrence surge reached a maximum 1.6 years after surgery. The curve subsequently declined until reaching a nadir at 7.2 years. A second peak occurred at 8.8 years. An analysis of clinical-pathological factors demonstrated that this double-peaked pattern was present in several subgroups.

Conclusions

The presence of a double-peaked pattern indicates that there is a predictable temporal distribution of the recurrence hazard of early-stage NSCLC. The annual recurrence hazard may be an effective method of selecting patients at high risk of recurrence, who may benefit from adjuvant therapy.     

Serum S100B,Lactate Dehydrogenase and Brain Metastasis Are Prognostic Factors in Patients with Distant Melanoma Metastasis and Systemic Therapy

Background

Prognostic factors of melanoma with distant metastasis and systemic treatment are only poorly established. This study aimed to analyse the impact of S100B, lactate dehydrogenase (LDH) and the type of treatment on survival in advanced patients receiving systemic treatment.

Patients and Methods

We analysed overall survival of 499 patients from the university department of dermatology in Tuebingen, Germany, with unresectable melanoma at the time point of initiation of first-line systemic therapy. Only patients who started treatment between the years 2000 and 2010 were included. Disease-specific survival was calculated by bivariate Kaplan Meier survival probabilities and multivariate Cox hazard regression analysis.

Results

In univariate analysis LDH, S100B, the site of distant metastasis (soft tissue vs. lung vs. other visceral), the presence of brain metastases and the type of treatment (monochemotherapy, polychemotherapy, immunotherapy or biochemotherapy) were associated with overall survival (all p<0.001). In multivariate analysis LDH (Hazard ratio [HR] 1.6 [1.3–2.1]; p<0.001), S100B (HR 1.6 [1.2–2.1]; p<0.001) and the presence of brain metastases (HR 1.5 [1.1–1.9]; p = 0.009), but not the type of treatment had significant independent impact. Among those factors normal S100B was the best indicator of long-term survival, which was 12.3% after 5 years for this subgroup.

Conclusion

Serum S100B is a prognostic marker predicting survival at the time of initiation of first-line treatment in unresectable melanoma patients. Compared to the other independent factors LDH and the presence of brain metastases it is most appropriate to predict long-term survival and requires further prospective investigation in patients treated with new and more potent drugs in metastatic melanoma.     

Time course and pattern of metastasis of cutaneous melanoma differ between men and women

Background

This study identified sex differences in progression of cutaneous melanoma.

Methodology/Principal Findings

Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7% of men and 29.2% of women (P<0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3% of men and 23.2% of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95% CI: 1.0–1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95% CI: 4.2–7.1 for distant metastasis vs. satellite/in-transit recurrence, P<0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4–2.5) for men compared with 15.3% (95% CI: 11.1–19.5; P = 0.008) for women.

Conclusions/Significance

Both, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic factors may be responsible for these sex differences.     

Gender Differences in Survival and the Use of Primary Care Prior to Diagnosis of Three Cancers: An Analysis of Routinely Collected UK General Practice Data

Objective

To explore whether there are gender differences in the number of GP recorded cases, the probability of survival and consulting pattern prior to diagnosis amongst patients with three non-sex-specific cancers.

Design

Cross sectional study.

Setting

UK primary care.

Subjects

12,189 patients aged 16 years or over diagnosed with colorectal cancer (CRC), 11,081 patients with lung cancer and 4,352 patients with malignant melanoma, with first record of cancer diagnosis during 1997–2006.

Main outcome measures

Cancer cases recorded in primary care; probability of survival following diagnosis; and number of GP contacts within the 24 months preceding diagnosis.

Results

From 1997–2006, overall rates of GP recorded CRC and lung cancer cases recorded were higher in men than in women, but rates of malignant melanoma were higher in women than in men. Gender differences in survival were small; 49% of men and 53% of women survived at least 5 years following CRC diagnosis; 9% of men and 12% of women with lung cancer, and 77% of men and 86% of women with malignant melanoma. The adjusted male to female relative hazard ratio of death in all patients was 1.20 (95%CI 1.13–1.30), 1.24 (95%CI 1.16–1.33) and 1.73 (95%CI 1.51–2.00) for CRC, lung cancer and malignant melanoma respectively. However, gender differences in the relative risk were much smaller amongst those who died during follow-up. For each cancer, there was little evidence of gender difference in the percentage who consulted and the number of GP contacts made within 24 months prior to diagnosis.

Conclusions

This study found that patterns of consulting prior to cancer diagnosis differed little between two genders, providing no support for the hypothesis that gender differences in survival are explained by gender differences in consultation for more serious illness, and suggests the need for a more critical view of gender and consultation.     

Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone in Patients with Malignant Melanoma: A Meta-Analysis

Background

Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma.

Methods

We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events.

Results

Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27–2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14–1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10–1.36), vomiting (combined RR = 1.73, 95% CI: 1.41–2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42–2.16) compared to the group for DTIC alone.

Conclusion

These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.     

Positive Lymph Node Metastasis Has a Marked Impact on the Long-Term Survival of Patients with Hepatocellular Carcinoma with Extrahepatic Metastasis

Background

The prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastasis is extremely poor. However, what is the main risk factor for survival remains unclear for these patients. We aimed to find out the relative frequency, incidence and locations of extrahepatic metastases and the risk factors of long-term survival of the patients.

Methods

132 HCC patients with extrahepatic metastasis diagnosed by ¹⁸F-FDG PET/CT and conventional workup were enrolled into this study. The incidence and locations of extrahepatic metastases were summarized, and the related risk factors of overall survival were analyzed.

Results

The most frequent extrahepatic metastatic sites were lymph nodes in 72 (54.5%), bone in 33 (25.0%) and lung in 28 (21.2%) patients. On univariate analysis, prothrombin time, Child-Pugh grade, portal/hepatic vein invasion and lymph node metastasis were independent risk factors of overall survival. On multivariate analysis, lymph node metastasis was the only independent risk factor of overall survival. The cumulative survival rates at 1- and 3-years after diagnosis of extrahepatic metastasis of HCC were 34.4% and 9.3%, respectively. The median survival time was 7 months (range 1 ∼38 months). The median survival time for patients with or without lymph node metastasis were 5 months (range 1∼38 months) and 12 months (range 1∼30 months), respectively (P = 0.036).

Conclusions

This study showed lymph nodes to be the most frequent site of extrahepatic metastases for primary HCC. Lymph node metastasis was the main risk factor of overall survival in patients with HCC with extrahepatic metastasis.     

Cytoplasmic Skp2 expression is increased in human melanoma and correlated with patient survival

Background

S-phase kinase protein 2 (Skp2), an F-box protein, targets cell cycle regulators via ubiquitin-mediated degradation. Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival. In melanoma, however, the prognostic significance of subcellular Skp2 expression remains controversial.

Methods

To investigate the role of Skp2 in melanoma development, we constructed tissue microarrays and examined Skp2 expression in melanocytic lesions at different stages, including 30 normal nevi, 61 dysplastic nevi, 290 primary melanomas and 146 metastatic melanomas. The TMA was assessed for cytoplasmic and nuclear Skp2 expression by immunohistochemistry. The Kaplan-Meier method was used to evaluate the patient survival. The univariate and multivariate Cox regression models were performed to estimate the harzard ratios (HR) at five-year follow-up.

Results

Cytoplasmic but not nuclear Skp2 expression was gradually increased from normal nevi, dysplastic nevi, primary melanomas to metastatic melanomas. Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II–IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005). Increased cytoplasmic Skp2 expression was associated with a poor five-year disease-specific survival of patients with primary melanoma (P = 0.018) but not metastatic melanoma (P>0.05).

Conclusion

This study demonstrates that cytoplasmic Skp2 plays an important role in melanoma pathogenesis and its expression correlates with patient survival. Our data indicate that cytoplasmic Skp2 may serve as a potential biomarker for melanoma progression and a therapeutic target for this disease.     

The Outcome of Ipsilateral Hemihepatectomy in Mucin-Producing Bile Duct Tumors

Background

Mucin-producing bile duct tumors (MPBTs) are unusual, and we present our experience with nine surgically proven cases.

Methods

Between November 2002 and November 2012, 9 patients with surgically proven MPBTs (including history of relevant hepatobiliary surgery in 6 patients) were encountered. Their clinical, imaging, and surgical findings were reviewed.

Results

The most common symptom is intermittent jaundice, which occurs in seven patients. The diagnostic specificity was 77.8% by preoperative Magnetic Resonance Cholangiopancreatography (MRCP). All the patients underwent ipsilateral hemihepatectomy or remnant hemihepatectomy, accompanied caudate lobectomy in one case and concomitant Roux-en-Y choledochojejunostomy in four cases. Postoperative course was uneventful. One patient, who had intra-abdominal recurrence 59 months after surgery, was received reoperation without recurrence at the last follow-up. The remaining eight patients were alive without disease recurrence.

Conclusion

Based on our follow up of 9 cases that were surgically treated for MPBTs, we conclude that ipsilateral hemihepatectomy is a safe surgical procedure with an observed recurrence risk of 11.1% and all long-term survival.     

Adoptive immunotherapy in postoperative hepatocellular carcinoma: a systemic review

Purpose

The effectiveness of immunotherapy for postoperative hepatocellular carcinoma patients is still controversial. To address this issue, we did a systemic review of the literatures and analyzed the data with emphasis on the recurrence and survival.

Methods

We searched six randomized controlled trials that included adoptive immunotherapy in the postoperative management of hepatocellular carcinoma and compared with non-immunotherapy postoperation. A meta-analysis was carried out to examine one- and 3-year recurrence and survival.

Results

The overall analysis revealed significantly reduced risk of 1-year recurrence in patients receiving adoptive immunotherapy (OR = 0.35; 95% CI, 0.17 to 0.71; p = 0.003), in that the risk of 3-year recurrence with a pooled OR estimated at 0.31 (95% CI 0.16 to 0.61; p = 0.001). However, no statistically significant difference was observed for 3-year survival between groups with adoptive immunotherapy and without adjuvant treatment (OR = 0.91; 95% CI, 0.45 to 1.84; P = 0.792).

Conclusions

Adjuvant immunotherapy with cytokine induced killer cells or lymphokine activated killer cells may reduce recurrence in postoperative hepatocellular carcinoma patients, but may not improve survival.     

Oligo- and Polymetastatic Progression in Lung Metastasis(es) Patients Is Associated with Specific MicroRNAs

Rationale

Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy.

Methods

We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤5 initial metastases resected with curative intent.

Results

Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset.

Conclusion

Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.     

Retrospective Analysis of 234 Nasopharyngeal Carcinoma Patients with Distant Metastasis at Initial Diagnosis: Therapeutic Approaches and Prognostic Factors

Purpose

The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.

Methods

A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses.

Results

The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS.

Conclusion

A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.     

Feasibility of Tomotherapy-Based Image-Guided Radiotherapy for Locally Advanced Oropharyngeal Cancer

Purpose

The study aims to assess the feasibility of tomotherapy-based image-guided (IGRT) radiotherapy for locally advanced oropharyngeal cancer. A retrospective review of 33 patients undergoing concurrent chemoradiation for locally advanced oropharyngeal cancers was conducted. Radiotherapy planning, treatment toxicity and loco-regional control were assessed.

Results

At a median follow-up of 32 months (6–47 months), no patient developed loco-regional recurrence. Two patients (6%) developed distant metastases. Grade 3–4 acute toxicity was respectively 72% and 25% for mucositis and gastrointestinal toxicity. Two patients (6%) had long-term dependence on tube feedings. Dose-volume histogram demonstrated excellent target volume coverage and low radiation dose to the organs at risk for complications.

Conclusions and clinical relevance

IGRT provides excellent loco-regional control but acute toxicity remains significant and needs to be addressed in future prospective trials. The feasibility of Tomotherapy to decrease radiation dose to the normal tissues merits further investigations.     

Radio-chemotherapy in anal cancer: Institutional experience at a large radiation oncology center in Chile

Aim

In this article the aim is to provide a concise narrative review and inform the institutional experience at a referral center in Chile with the use of radio-chemotherapy in anal cancer.

Background

Cancer of the anus and anal canal is mainly a loco-regional disease. For years the standard of care has been concomitant radio-chemotherapy, which permits organ preservation and better local control than alternative surgical procedures.

Materials and methods

A retrospective analysis of 44 patients treated between 2002 and 2010 was performed. Local recurrence, distant recurrence and overall survival were analyzed with the Kaplan–Meier method. Relevant groups where compared with the log-rank test and univariate analysis were done with the Cox proportional hazards model.

Results

Median follow-up of the cohort was 56 months, with a minimum follow-up of at least 24 months. There was a significant difference between clinical stages in disease free survival (log-rank trend p < 0.001), and a significant difference in overall survival (OS) when comparing clinical stages that were grouped in stage I–IIIa and IIIB (log-rank p = 0.001). On univariate analysis, age older than 60, having received full treatment and dose above 45 Gy were all significantly related to OS (p < 0.05). An overall survival of 45% and disease free survival of 45% at 5 years were found in our series.

Conclusions

Our findings show that results at the Instituto de Radiomedicina in Chile are comparable to published literature. Dismal results in stage IIIb cases indicate much work remains in therapies to achieve loco-regional control in locally advanced cases.     

Germline Variation in Colorectal Risk Loci Does Not Influence Treatment Effect or Survival in Metastatic Colorectal Cancer

Background

Colorectal cancer (CRC) risk is partly conferred by common, low-penetrance single nucleotide polymorphisms (SNPs). We hypothesized that these SNPs are associated with outcomes in metastatic CRC.

Methods

Six candidate SNPs from 8q24, 10p14, 15q13, 18q21 were investigated for their association with response rate (RR), time to progression (TTP) and overall survival (OS) among 524 patients treated on a phase III clinical trial of first-line chemotherapy for metastatic CRC.

Results

rs10795668 was weakly associated with TTP (p = 0.02), but not RR or OS. No other SNPs carried statistically significant HRs for any of the primary outcomes (RR, TTP or OS).

Conclusion

Common low-penetrance CRC risk SNPs were not associated with outcomes among patients with metastatic CRC.     

The Influence of Hepatitis B Viral Load and Pre-S Deletion Mutations on Post-Operative Recurrence of Hepatocellular Carcinoma and the Tertiary Preventive Effects by Anti-Viral Therapy

Background

Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.

Aims

To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.

Methods

A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels, mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.

Results

After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >10⁶ copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.

Conclusions

Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.     

Outcome of a multimodal therapy of a recurrent adenocarcinoma arising from Caesarean section scar endometriosis—A case report

Background

Endometriosis occurring in surgical scars is a well-described entity. Malignant transformation of endometriosis is a rare event, with most cases belonging to adenocarcinoma. The initial surgical treatment is a method of choice. Due to lack of therapeutic recommendations, adjuvant therapy and recurrence management are a great challenge for oncologists.

Aim

The aim of this paper was to present a long-term survival as the outcome of multimodal therapy in the patient with recurrent adenocarcinoma arising from Caesarean section scar endometriosis.

Case

We present the case of a woman with recurrent adenocarcinoma arising from Caesarean section scar endometriosis. The disease was first diagnosed in September 1997 at age 43. The patient underwent abdominal hysterectomy with tumour excision. Due to a local recurrence after 4 years, tumour excision with abdominal wall repair using a plastic mesh, regional lymphadenectomy, bilateral salpingo-ovariectomy and adjuvant radiotherapy for the pelvic region with local boost were performed; in addition hormontherapy with medroxyprogesterone was started. Because of a recurrent pelvic tumour, chemotherapy, further local palliative radiotherapy and brachytherapy were administered. Subsequently distant metastases in bilateral axillary lymph nodes were diagnosed and palliative radiotherapy was performed. The patient died of morbus neoplasmaticus generalisatus in September 2008. The follow-up period had been 132 months.

Conclusion

This paper is, to our knowledge, the only report in literature that presents a long-term survival as the outcome of multimodal therapy in the patient with this rare diagnosis. Further reports of new cases can help establish optimal treatment guidelines.     

LC/MS-Based Quantitative Proteomic Analysis of Paraffin-Embedded Archival Melanomas Reveals Potential Proteomic Biomarkers Associated with Metastasis

Background

Melanoma metastasis status is highly associated with the overall survival of patients; yet, little is known about proteomic changes during melanoma tumor progression. To better understand the changes in protein expression involved in melanoma progression and metastasis, and to identify potential biomarkers, we conducted a global quantitative proteomic analysis on archival metastatic and primary melanomas.

Methodology and Findings

A total of 16 metastatic and 8 primary cutaneous melanomas were assessed. Proteins were extracted from laser captured microdissected formalin fixed paraffin-embedded archival tissues by liquefying tissue cells. These preparations were analyzed by a LC/MS-based label-free protein quantification method. More than 1500 proteins were identified in the tissue lysates with a peptide ID confidence level of >75%. This approach identified 120 significant changes in protein levels. These proteins were identified from multiple peptides with high confidence identification and were expressed at significantly different levels in metastases as compared with primary melanomas (q-Value<0.05).

Conclusions and Significance

The differentially expressed proteins were classified by biological process or mapped into biological system networks, and several proteins were implicated by these analyses as cancer- or metastasis-related. These proteins represent potential biomarkers for tumor progression. The study successfully identified proteins that are differentially expressed in formalin fixed paraffin-embedded specimens of metastatic and primary melanoma.