Curing pancreatic cancer.

The distinct biology of pancreatic cancer with aggressive and early invasive tumor cells, a tumor promoting microenvironment, late diagnosis, and high therapy resistance poses major challenges on clinicians, researchers, and patients. In current clinical practice, a curative approach for pancreatic cancer can only be offered to a minority of patients and even for those patients, the long-term outcome is grim. This bitter combination will eventually let pancreatic cancer rise to the second leading cause of cancer-related mortalities. With surgery being the only curative option, complete tumor resection still remains the center of pancreatic cancer treatment. In recent years, new developments in neoadjuvant and adjuvant treatment have emerged. Together with improved perioperative care including complication management, an increasing number of patients have become eligible for tumor resection. Basic research aims to further increase these numbers by new methods of early detection, better tumor modelling and personalized treatment options. This review aims to summarize the current knowledge on clinical and biologic features, surgical and non-surgical treatment options, and the improved collaboration of clinicians and basic researchers in pancreatic cancer that will hopefully result in more successful ways of curing pancreatic cancer.

The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer.

BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.

Towards standardization of management of gallbladder carcinoma with obstructive jaundice: Analysis of 113 cases over 10 years at a single institution.

BACKGROUND: Presence of jaundice in gallbladder carcinoma (GBC) is considered a sign of inoperability with no defined treatment pathways. METHODS: Retrospective analysis of all surgically treated GBC patients from January 2010 to December 2019 was performed for evaluating etiology of obstructive jaundice, resectability, postoperative morbidity, mortality, disease-free survival (DFS) and overall survival (OS). RESULTS: Out of 954 patients, 521 patients (54.61%) were locally advanced gallbladder carcinoma (LAGBC: Stage III and IV) and 113 patients (11.84%) had jaundice at presentation. Thirty-four (30%) patients had benign cause of obstructive jaundice. Median OS of the whole cohort (n=113) was 22 months (16.5-27.49 months) with resectability rate of 62% (70/113). Median OS of curative resection group (n=70) was 32 months and DFS was 25 months. Treatment completion was achieved in 30% (n= 21/70) patients with median OS of 46 months and median DFS of 27 months. Isolated bile duct infiltration subgroup fared the best with median OS of 74 months with a 5-year survival of 66.7%. CONCLUSION: Surgical resection as a part of multimodality treatment improves survival in carefully selected locally advanced gallbladder cancer patients with jaundice. Early introduction of systemic therapy is the key in the management of this disease with aggressive tumor biology.

Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial.

BACKGROUND: Obesity is a risk factor for breast cancer (BC) development, recurrence, and death. In view of this, we aimed to investigate the clinical value of obesity in BC patients treated with anti-HER2 therapies in the NeoALTTO trial, which randomized 455 patients to neo-adjuvant lapatinib, trastuzumab, or their combination plus paclitaxel. METHODS: Patients were classified according to their basal body mass index (BMI) into underweight (< 18.5 kg/m2), normal (≥ 18.5; < 25 kg/m2), overweight (≥ 25; < 30 kg/m2), and obese (≥ 30 kg/m2) WHO categories. Univariate and multivariate logistic regression analyses were performed using BMI as a categorical variable. Pathological complete response (pCR) and event-free survival (EFS) were the NeoALTTO primary and secondary outcomes, respectively. RESULTS: Among 454 patients analyzed, 14 (3%), 220 (48%), 137 (30%), and 83 (18%) were classified as underweight, normal weight, overweight, and obese, respectively; 231 (51%) and 223 (49%) had hormone receptor (HR)-positive and HR-negative primary tumors; 160 (35%) achieved pCR. In the overall patient population, no association was found between BMI groups and pCR, as we reported pCR rates of 57.1%, 35%, 30.7%, and 39.8% in underweight, normal weight, overweight, and obese cases, respectively. In contrast, in HR-positive tumors, overweight or obesity was generally associated with decreased likelihood of achieving a pCR independently of other clinical variables, including planned surgery, nodal status, and tumor size (odds ratio [OR] = 0.55, 95%CI 0.30-1.01, as compared to normal or underweight; p = 0.053); notably, no differential effect of BMI with respect to pCR was observed in HR-negative cases (odds ratio [OR] = 1.30, 95%CI 0.76-2.23, as compared to normal or underweight; p = 0.331), resulting in a statistically significant interaction between BMI and HR status (p = 0.036). There was no association between BMI and EFS neither in the overall nor in the HR-positive population, but this analysis was under-powered. CONCLUSIONS: NeoALTTO patients overweight or obese at baseline and with HR-positive primary BC appeared less likely to achieve pCR after neo-adjuvant anti-HER2 therapies. This finding paves the way to future research in targeting the interplay between HER2/HR signaling and metabolism.

Primary malignant melanoma of the genitourinary tract: case series of a rare form of primary mucosal melanoma.

Primary malignant melanoma of the genitourinary tract is extremely rare. We present two such cases in elderly Caucasian females. An 81-year-old female with urinary retention and polypoid urinary bladder mass and a 72-year-old female with gross hematuria and urethral caruncle. After thorough evaluation, they were both eventually diagnosed with primary urogenital melanoma (SOX10 and MART1-positive in tumor cells). In both cases, the presence of melanoma-in-situ and absence of primary melanoma in other sites were consistent with primary urogenital melanoma. Immunotherapy with PD-1 inhibitors and use of neoadjuvant and adjuvant treatment are promising, as treatment guidelines remain unclear and overall survival is low. Additional clinical reporting of primary urogenital melanomas can help in better understanding and ultimately treating it.

Primary melanomas of the bladder and urinary tract are rare and usually deadly. They represent only 0.2% of all melanomas, including melanomas of skin. They can be difficult to diagnose and treat due to how rare they are and the lack of clear treatment guidelines. We present two cases of elderly Caucasian women who were unexpectedly diagnosed with primary melanoma cancers of the bladder and urinary tract after having surgery and analyzing tissue that was removed. Both tissue samples had features specific to melanoma and there was no cancer in any other organ, thus making them primary melanomas of the bladder and urinary tract. Current treatment approaches with surgery and chemotherapy have not improved the survival outcomes and prognosis associated with this disease, but treatment before and after surgery as well as cancer treatments that harness the person's own immune system are promising. By reporting additional clinical experiences of this often fatal disease, we hope it can be better understood and appropriately managed in the future.

Neo-Adjuvant Treatment in Primary Resectable Pancreatic Cancer: A Systematic Review and PRISMA-Compliant Updated Metanalysis of Oncological Outcomes.

BACKGROUND: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. METHODS: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. RESULTS: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72-0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56-0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32-0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23-2.36) were also found in patients treated with NAT, despite high heterogeneity. CONCLUSIONS: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required.

Current Advances in Papillary Craniopharyngioma: State-Of-The-Art Therapies and Overview of the Literature.

Craniopharyngiomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior due to their high rate of recurrence and long-term morbidity. Craniopharyngiomas are classically distinguished into two histological types (adamantinomatous and papillary), which have been recently considered by the WHO classification of CNS tumors as two independent entities, due to different epidemiological, radiological, histopathological, and genetic patterns. With regard to papillary craniopharyngioma, a BRAF V600 mutation is detected in 95% of cases. This genetic feature is opening new frontiers in the treatment of these tumors using an adjuvant or, in selected cases, a neo-adjuvant approach. In this article, we present an overview of the more recent literature, focusing on the specificities and the role of oncological treatment in the management of papillary craniopharyngiomas. Based on our research and experience, we strongly suggest a multimodal approach combining clinical, endocrinological, radiological, histological, and oncological findings in both preoperative workup and postoperative follow up to define a roadmap integrating every aspect of this challenging condition.

Systemic Therapy De-Escalation in Early-Stage Triple-Negative Breast Cancer: Dawn of a New Era?

Early-stage triple negative breast cancer (TNBC) has been traditionally treated with surgery, radiation, and chemotherapy. The current standard of care systemic treatment of early-stage II and III TNBC involves the use of anthracycline-cyclophosphamide and carboplatin-paclitaxel with pembrolizumab in the neoadjuvant setting followed by adjuvant pembrolizumab per KEYNOTE-522. It is increasingly clear that not all patients with early-stage TNBC need this intensive treatment, thus paving the way for exploring opportunities for regimen de-escalation in selected subgroups. For T1a tumors (≤5 mm), chemotherapy is not used, and for tumors 6-10 mm (T1b) in size with negative lymph nodes, retrospective studies have failed to show a significant benefit with chemotherapy. In low-risk patients, anthracycline-free chemotherapy may be as effective as conventional therapy, as shown in some studies where replacing anthracyclines with carboplatin has shown non-inferior results for pathological complete response (pCR), which may form the backbone of future combination therapies. Recent advances in our understanding of TNBC heterogeneity, mutations, and surrogate markers of response such as pCR have enabled the development of multiple treatment options in the (neo)adjuvant setting in order to de-escalate treatment. These de-escalation studies based on tumor mutational status, such as using Poly ADP-ribose polymerase inhibitors (PARPi) in patients with BRCA mutations, and new immunotherapies such as PD1 blockade, have shown a promising impact on pCR. In addition, the investigational use of (bio)markers, such as high levels of tumor-infiltrating lymphocytes (TILs), low levels of tumor-associated macrophages (TAMs), and complete remission on imaging, also look promising. In this review, we cover the current standard of care systemic treatment of early TNBC and review the opportunities for treatment de-escalation based on clinical risk factors, biomarkers, mutational status, and molecular subtype.

Delayed Surgery after Neoadjuvant Treatment for Rectal Cancer Does Not Lead to Impaired Quality of Life, Worry for Cancer, or Regret.

Non operative management of complete clinical responders after neoadjuvant treatment for rectal cancer enjoys an increasing popularity because of the increased functional outcome results. Even a near complete response can evolve in a cCR, and therefore further delaying response assessment is accepted. However, up to 40% of patients will develop a regrowth and will eventually require delayed surgery. It is presently unknown if and to what extent quality of life of these patients is affected, compared to patients who undergo immediate surgery. Between January 2015-May 2020, 200 patients were treated with neoadjuvant therapy of whom 94 received TME surgery. Fifty-one (59%) of 87 alive patients returned the questionnaires: 33 patients who underwent immediate and 18 patients who underwent delayed surgery. Quality of life was measured through the QLQ-C30, QLQ-CR29, and Cancer Worry Scale questionnaires. Regret to participate in repeated response assessment protocol was assessed through the Decision Regret Scale. Exploratory factor analysis (EFA) and a 'known groups comparison' was performed to assess QLQ questionnaires validity in this sample. Higher mean physical function scores (89.2 vs. 77.6, p = 0.03) were observed in the immediate surgery group, which lost significance after correction for operation type (p = 0.25). Arousal for men was higher in the delayed surgery group (20.0 vs. 57.1, p = 0.02). There were no differences between surgical groups for the other questionnaire items. Worry for cancer was lower in the delayed surgery group (10.8 vs. 14.0, p = 0.21). Regret was very low (12-16%). EFA reproduced most QLQ C-30 and CR29 subscales with good internal consistency. Quality of life is not impaired in patients undergoing delayed TME surgery after neoadjuvant treatment for rectal cancer. Moreover, there is very low regret and no increase in worry for cancer. Therefore, from a quality of life perspective, this study supports a repeated response assessment strategy after CRTx for rectal carcinoma to identify all complete responders.

Prognostic Role of Tumor Budding in Breast Cancer Patients Receiving Neo-Adjuvant Therapy.

BACKGROUND: Isolated tumor cells or small clusters of tumor cells observed in the vicinity of the main tumor mass in pathology sections, termed tumor budding, are common in cancers and have been associated with prognosis in some settings. This study examined the clinical associations and treatment efficacy implications of tumor budding in breast cancer patients receiving neo-adjuvant therapy. METHODS: Breast cancer patients that received neo-adjuvant therapy before definitive surgical treatment in a single cancer center over a 7-year period were included, and their records were reviewed. Data extracted included patient demographics, tumor characteristics and pathologic response to treatment at surgery. The initial breast cancer biopsy before any therapy was reviewed by two pathologists, and a hot spot area was evaluated for tumor budding (defined as 1 to 5 cancer cells observed detached from the main tumor mass). RESULTS: Seventy-five patients who received neo-adjuvant therapy (73 received chemotherapy and 2 received hormonal therapy) were included. Tumor budding was observed in two-thirds of the patients. There were no significant differences in patient (age and menopause status) and tumor (stage, histology and molecular sub-type equivalent) characteristics between the group that had tumor budding and the group that did not have tumor budding in the pre-treatment biopsy. Likewise, no statistically significant differences were observed in the frequency of complete or partial responses between the two groups. CONCLUSION: In this cohort of breast cancer patients receiving neo-adjuvant therapy, tumor budding was frequent, but it was not associated with tumor characteristics or pathologic responses to treatment. The value of tumor budding as a prognostic factor in the neo-adjuvant setting within the general breast cancer population could not be confirmed, but such a value in specific sub-groups deserves further investigation, given the pathophysiologic rationale and data from other settings.

Pre-clinical modelling of rectal cancer to develop novel radiotherapy-based treatment strategies.

Pre-operative chemoradiotherapy reduces local recurrence rates in locally advanced rectal cancer. 10-20% of patients undergo complete response to chemoradiotherapy, however, many patients show no response. The mechanisms underlying this are poorly understood; identifying molecular and immunological factors underpinning heterogeneous responses to chemoradiotherapy, will promote development of treatment strategies to improve responses and overcome resistance mechanisms. This review describes the advances made in pre-clinical modelling of colorectal cancer, including genetically engineered mouse models, transplantation models, patient derived organoids and radiotherapy platforms to study responses to chemoradiotherapy. Relevant literature was identified through the PubMed and MEDLINE databases, using the following keywords: rectal cancer; mouse models; organoids; neo-adjuvant treatment; radiotherapy; chemotherapy. By delineating the advantages and disadvantages of available models, we discuss how modelling techniques can be utilized to address current research priorities in locally advanced rectal cancer. We provide unique insight into the potential application of pre-clinical models in the development of novel neo-adjuvant treatment strategies, which will hopefully guide future clinical trials.

Morphological Estimation of Cellularity on Neo-Adjuvant Treated Breast Cancer Histological Images.

This paper describes a methodology that extracts key morphological features from histological breast cancer images in order to automatically assess Tumour Cellularity (TC) in Neo-Adjuvant treatment (NAT) patients. The response to NAT gives information on therapy efficacy and it is measured by the residual cancer burden index, which is composed of two metrics: TC and the assessment of lymph nodes. The data consist of whole slide images (WSIs) of breast tissue stained with Hematoxylin and Eosin (H&E) released in the 2019 SPIE Breast Challenge. The methodology proposed is based on traditional computer vision methods (K-means, watershed segmentation, Otsu's binarisation, and morphological operations), implementing colour separation, segmentation, and feature extraction. Correlation between morphological features and the residual TC after a NAT treatment was examined. Linear regression and statistical methods were used and twenty-two key morphological parameters from the nuclei, epithelial region, and the full image were extracted. Subsequently, an automated TC assessment that was based on Machine Learning (ML) algorithms was implemented and trained with only selected key parameters. The methodology was validated with the score assigned by two pathologists through the intra-class correlation coefficient (ICC). The selection of key morphological parameters improved the results reported over other ML methodologies and it was very close to deep learning methodologies. These results are encouraging, as a traditionally-trained ML algorithm can be useful when limited training data are available preventing the use of deep learning approaches.

Tolerability of Oxaliplatin-based Neoadjuvant Chemoradiotherapy in Elderly Locally Advanced Rectal Cancer Patients: A Case-control Study of a Real-life Experience.

BACKGROUND/AIM: The aim of this study was to delineate clinical criteria to safely select elderly patients who can benefit from adding oxaliplatin to 5-fluoruracil-based neo-adjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) management. PATIENTS AND METHODS: This is a single-institutional case-control study on LARC patients who received intensified neo-adjuvant CRT, between January 2007 and December 2014. Data concerning patient characteristics, treatment details and adverse events were reviewed and analyzed in two settings: young patients (<65 years) and elderly (≥65 years). A binary logistic model was applied to analyze the potential interaction between clinical variables and severe toxicity risk. RESULTS: In total, 100 consecutive LARC patients were included. Mean age was 63.6 years and 55% (n=55) of the patients had adult comorbidity evaluation-27 (ACE-27) score ≥1. Most cancers (81%) were lymph node positive at diagnosis. Overall, ≥5 cycles of oxaliplatin were administered to 92 patients (92%). Only 17 patients (17%) reported grade ≥3 toxicity. The elderly group did not experience significantly higher severe toxicity than the young group. ACE-27 score ≥1 was the only variable independently associated with a higher severe toxicity. The 5-year overal survival (OS) rates were 64.1% and 89.2% in the elderly and young cohort, respectively. CONCLUSION: Elderly LARC patients can be safely treated with intensified neo-adjuvant CRT.

Long-term outcomes in ypT0 rectal cancers: An international multi-centric investigation on behalf of Italian Society of Surgical Oncology Young Board (YSICO).

AIM: To investigate the outcome and pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neo-adjuvant treatment. METHODS: Young surgeons <40 years old affiliated to the Italian Society of Surgical Oncology (YSICO) from 13 referral centers for colorectal cancer treatment, were invited to participate a retrospective study. Records from patients treated from 2005 to 2015 with a pathological diagnosis of ypT0/ypTis were retrieved and pooled in a common data-base for statistical purposes. All clinical and pathological variables were reviewed. Univariate and multivariate analyses were conducted with the end-point of survivals. RESULTS: Two hundreds and sixty-one patients were analyzed including 237 ypT0 and 24 ypTis. Nodal positive patients were 8.7%. More than sixty-six percent of the patients did not perform adjuvant chemotherapy, with a statistical difference comparing N0 versus N+ patients (66.8% vs 40.9%, p 0.02). Mean follow-up was of 47.6 months. Twenty-two relapses were observed, 91.6% at a distant site. The mean time to recurrence was of 35.3 months. On univariate analysis, the use of adjuvant chemotherapy correlated with better OS exclusively in ypT0N + patients and not in ypT0N0. Univariate and multivariate analyses documented nodal positivity as the only prognostic factor correlated with a worse OS. CONCLUSION: Recurrences were mostly diagnosed at a distant site and within the third year of follow-up. Nodal positivity was the only variable independently correlated with a worse OS. Univariate analysis documented a benefit for the use of adjuvant chemotherapy treatment exclusively in ypT0N + rectal cancers.

Trastuzumab in combination with weekly paclitaxel and carboplatin as neo-adjuvant treatment for HER2-positive breast cancer: The TRAIN-study.

AIM: To determine the efficacy and safety of an anthracycline-free neo-adjuvant regimen consisting of weekly paclitaxel, carboplatin and trastuzumab in HER2-positive breast cancer. PATIENTS AND METHODS: Patients with stage II or III HER2-positive breast cancer received weekly paclitaxel ([P], 70 mg/m2), trastuzumab ([T], 2 mg/kg, loading dose 4 mg/kg) and carboplatin ([C], AUC = 3 mg ml-1 min) for 24 weeks. In weeks 7, 8, 15, 16, 23 and 24, trastuzumab was administered without chemotherapy. The primary end-point was pathologic complete response in the surgical resection specimen, defined as the absence of invasive tumour cells in breast and axilla. RESULTS: One hundred and eleven patients were included in the study, and 108 were evaluable for the primary end-point. The pathologic complete response rate was 43% (95% confidence interval [CI]: 33-52). Median follow-up was 52 months, and the 3-year event-free survival was 88% (95% CI: 82-94), and the 3-year overall survival was 92% (95% CI: 88-98). The most common grade 3-4 adverse events were neutropenia (67%) and thrombocytopenia (43%). Less than five percent of patients experienced febrile neutropenia. No symptomatic left ventricular systolic dysfunction was observed during neo-adjuvant treatment. CONCLUSION: An anthracycline-free neo-adjuvant regimen of weekly paclitaxel, trastuzumab and carboplatin is highly effective in HER2-positive breast cancer with manageable toxicity.

Stoma placement in obstructive rectal cancer prior to neo-adjuvant treatment and definitive surgery: A practical guideline.

INTRODUCTION: Mechanical bowel obstruction in rectal cancer is a common problem, requiring stoma placement to decompress the colon and permit neo-adjuvant treatment. The majority of patients operated on in our hospital are referred; after stoma placement at the referring centre without overseeing final type of surgery. Stoma malpositioning and its effects on rectal cancer care are described. METHODS: All patients who underwent surgery for locally advanced or locally recurrent rectal cancer between 2000 and 2013 in our tertiary referral centre were reviewed and included if they received a stoma before curative surgery. Patients with recurrent rectal cancer were only included if the stomas from the primary surgery had been restored. The main outcome measures are stoma malpositioning, postoperative and stoma-related complications. RESULTS: A total of 726 patients were included; of these, 156 patients (21%) had a stoma before curative surgery. In the majority of patients, acute or pending large bowel obstruction was the main indication for emergent stoma creation; some of the patients had tumour-related fistulae. In 53 patients (34%), the stoma required revision during definitive surgery. No significant differences were found regarding postoperative complications. CONCLUSION: One-third of the previously placed emergency stomas were considered to be located inappropriately and required revision. We were able to avoid increased complication rates in patients with a malpositioned stoma, however unnecessary surgery for an inappropriately placed stoma should be avoided to decrease patient inconvenience and risks. An algorithm is proposed for the placement of a suitable stoma.

Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives.

In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules.

Locally advanced rectal cancer: the importance of a multidisciplinary approach.

Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

Does a venous tumor thrombus exclude renal transitional cell carcinoma? Implications for neo-adjuvant treatment strategies.

BACKGROUND: A venous tumor thrombus (VTT) is well-known in renal cell carcinoma, but we experienced a series of five patients with VTT due to renal transitional cell carcinoma (TCC). Our study aimed to determine the incidence and clinical relevance of this entity. PATIENTS AND METHODS: From our prospectively-maintained tumor database, we identified 102 patients with renal TCC according to postoperative histology and analyzed the incidence of VTT in renal TCC from 1990 to 2010. RESULTS: Five out of 102 patients with TCC (5%) had a VTT. None of these five patients experienced gross haematuria and we presumed correct diagnosis preoperatively in one out of five patients. Univariate analysis revealed that TNM stage and resection status were inferior in the VTT group. All five patients from the VTT group died from their disease, with a median survival of 8.9 months. With regard to all diagnosed VTT, the effective incidence of vena cava involvement in RCC was 48-fold higher than in renal TCC. CONCLUSION: A VTT is very suggestive of renal cell carcinoma. However, before neo-adjuvant treatment, the diagnosis should be assured whenever there is doubt.