Time interval between neoadjuvant radio-chemotherapy and surgery in rectal cancer: is the long interval correct for all patients?

BACKGROUND: Optimal time between neoadjuvant radio-chemotherapy period and surgery remains controversial in patients with rectal cancer: an increasing number of studies show results in favor of a long interval. METHODS: We conducted a retrospective analysis of the cases of low-middle rectal adenocarcinoma undergoing neoadjuvant RT-CT and surgery: the primary endpoint was the complete pathological response rate and the secondary endpoint the rate of complications. We analyzed cases from 1/01/2003 to 31/12/2018 divided in two periods: from 2003 to 2010 (23 pts) and from 2011 to 2018 (23 pts). The two periods were characterized by two different surgical teams which use different time intervals (≤ vs. >8 weeks). RESULTS: The pCR rate is 21.7% in both groups; as regards the complications, the difference between the two groups is in grade IIIb: 8.7% in the first group and 17.4% in the second group (P=0.66). CONCLUSIONS: Although our study is based on a small number of patients, it shows the same rate of pCR with respect to two different time intervals; this suggests the need for studies based on the division of patients into subgroups and the evaluation of different time intervals in order to reach the best oncological outcomes.

Association of Obesity With Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis.

Importance: Obesity, defined as a body mass index (BMI) greater than 30, is associated with a significant increase in the risk of many cancers and in overall mortality. However, various studies have suggested that patients with cancer and no obesity (ie, BMI 20-25) have worse outcomes than patients with obesity. Objective: To assess the association between obesity and outcomes after a diagnosis of cancer. Data Sources: PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020. Study Selection: Studies reporting prognosis of patients with obesity using standard BMI categories and cancer were included. Studies that used nonstandard BMI categories, that were limited to children, or that were limited to patients with hematological malignant neoplasms were excluded. Screening was performed independently by multiple reviewers. Among 1892 retrieved studies, 203 (17%) met inclusion criteria for initial evaluation. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were reporting guideline was followed. Data were extracted by multiple independent reviewers. Risk of death, cancer-specific mortality, and recurrence were pooled to provide an adjusted hazard ratio (HR) with a 95% CI . A random-effects model was used for the retrospective nature of studies. Main Outcomes and Measures: The primary outcome of the study was overall survival (OS) in patients with cancer, with and without obesity. Secondary end points were cancer-specific survival (CSS) and progression-free survival (PFS) or disease-free survival (DFS). The risk of events was reported as HRs with 95% CIs, with an HR greater than 1 associated with a worse outcome among patients with obesity vs those without. Results: A total of 203 studies with 6 320 365 participants evaluated the association of OS, CSS, and/or PFS or DFS with obesity in patients with cancer. Overall, obesity was associated with a reduced OS (HR, 1.14; 95% CI, 1.09-1.19; P < .001) and CSS (HR, 1.17; 95% CI, 1.12-1.23; P < .001). Patients were also at increased risk of recurrence (HR, 1.13; 95% CI, 1.07-1.19; P < .001). Conversely, patients with obesity and lung cancer, renal cell carcinoma, or melanoma had better survival outcomes compared with patients without obesity and the same cancer (lung: HR, 0.86; 95% CI, 0.76-0.98; P = .02; renal cell: HR, 0.74; 95% CI, 0.53-0.89; P = .02; melanoma: HR, 0.74; 95% CI, 0.57-0.96; P < .001). Conclusions and Relevance: In this study, obesity was associated with greater mortality overall in patients with cancer. However, patients with obesity and lung cancer, renal cell carcinoma, and melanoma had a lower risk of death than patients with the same cancers without obesity. Weight-reducing strategies may represent effective measures for reducing mortality in these patients.

A systematic review of salvage therapies in refractory metastatic colorectal cancer.

PURPOSE: Established that the only approved agents in previously treated metastatic colorectal cancer (CRC) are trifluoridine/tipiracil and regorafenib, we conducted a systematic review of all the published phase 2-3 trials, with the scope to evaluate the benefit of any later-line regimens in refractory metastatic CRC. METHODS: Phase 2-3 studies that enrolled patients with stage IV disease receiving salvage therapies for refractory CRC were identified using electronic databases (Pubmed, EMBASE, and Cochrane Library). Clinical outcomes were pooled using a point estimates for the weighted values of median overall survival (OS), progression-free survival (PFS), response rate (ORR), stable disease rate (SD), and 6-month and 1-year OS. RESULTS: Overall, 7556 patients were included from 67 studies (n = 70 arms). Overall, the pooled ORR and SD were 15.4% (95% CI 13-18%) and 36.9% (95% CI 33.5-40.6%). Median PFS, 6-month and 1-year OS, and median OS were 3.2 (95% CI 2.9-3.3) months, 65.4% (95% CI 61.9-68.8%), 36% (95% CI 32.3-39.9%) and 8.8 (95% CI 8.3-9.2) months. Overall survival was different in the monochemotherapy, polychemotherapy, chemotherapy + targeted therapy, and targeted therapy alone arms (7.6, 9.5, 10.3, and 7.9 months, respectively, P for difference = 0.01). Median PFS were respectively 2.3, 3.9, 3.8, and 2.6, respectively (P for difference < 0.01). CONCLUSIONS: Overall, combination therapy (polychemotherapy with or without targeted agents) is associated with a higher control of disease and better outcome than approved agents. Treatment, if possible, should be personalized according to the patients' conditions, physician preference and molecular profile of disease.

Microsatellite Instability and Survival in Stage II Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: About 15-20% of colorectal cancers (CRCs) have deficiency in a mismatch repair (MMR) protein. MMR has a high level of microsatellite instability (MSI-H). We have conducted this review and meta-analysis to determine the prognostic role of MSI-H status in stage II CRC. MATERIALS AND METHODS: We searched PubMed, EMBASE, The Cochrane Library, Web of Science, and SCOPUS for studies reporting data on overall survival (OS) and disease-free or relapse-free survival (DFS or RFS) for MSI-H compared to microsatellite stable (MSS) CRC. RESULTS: A total of 39 studies were analysed, including 12,110 patients. MSI-H status was associated with a significantly reduced risk of death (HR=0.64, 95%CI=0.52-0.8, p<0.01) and relapse (HR=0.59, 95%CI=0.45-0.77, p<0.01) in stage II CRC. CONCLUSION: MSI-H represents an important prognostic determinant in stage II CRC and may be considered when estimating the risk of recurrence in stage II CRC.

Surgery or Locoregional Approaches for Hepatic Oligometastatic Pancreatic Cancer: Myth, Hope, or Reality?

Despite extensive research, pancreatic ductal adenocarcinoma (PDAC) remains a difficult-to-treat cancer associated with poor survival. Due to the known aggressive disease biology, palliative chemotherapy is the only routinely recommended treatment in the metastatic setting in patients with adequate performance status. However, in a subset of patients with oligometastatic disease, multimodality treatment with surgery and/or locoregional approaches may provide long-term disease control and prolong survival. In fact, in highly selected cases, median overall survival has been reported to extend to 56 months in patients treated with surgery. In particular, liver and extraregional nodal resections may provide long-term tumor control with acceptable morbidity. Current guidelines do not recommend surgery for patients with metastatic PDAC and, in the case of PDAC with oligometastases, there are no published randomized controlled trials regarding locoregional or surgical approaches. Here we review the literature on surgical and locoregional approaches including radiofrequency ablation, irreversible electroporation, and stereotactic body radiation, and focus on patients with hepatic oligometastatic pancreatic cancer. We provide a summary regarding survival outcomes, morbidity and mortality and discuss selection criteria that may be useful to predict the best outcomes for such strategies.

Risk of second primary tumors in GIST survivors: A systematic review and meta-analysis.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors arising in the gastrointestinal tract. Second primary tumors (SPTs) have been reported frequently, either synchronously or during follow-up, in patients diagnosed with GISTs. METHODS: We carried out an electronic search of PubMed, SCOPUS, Web of Science, EMBASE, and the Cochrane Library seeking articles investigating the incidence of SPTs in patients with concomitant GIST. All studies were evaluated for heterogeneity before meta-analysis and for publication bias. Pooled incidence rate was estimated using fixed- and random-effects models. Subsite of SPTs was also investigated. RESULTS: A total of 32 studies met the inclusion criteria, for a total of 19,627 patients with a diagnosis of GIST. The pooled prevalence of SPTs was 20%, with 14% and 3% being synchronous and metachronous tumors, respectively. We found a risk for several specific cancer sites, in particular gastrointestinal (5%) and genitourinary tract cancers (3%). The most frequently associated malignancies were: colorectal (17%), prostate (14%), gastric (9%), esophageal (5.5%), lung (5.4%), hepato-biliopancreatic (4.7%), breast (4.6%), lymphoma (4.4%), kidney (4.35%), and sarcomas (3.3%). Regression analyses revealed a significant positive association for all SPTs with follow-up and Miettinen risk. CONCLUSIONS: Our results indicate that 20% of patients with GIST experienced a SPT, primarily synchronously with a diagnosis of GIST. In particular, we observed an excess of incident gastrointestinal tumors. These findings have important implications for both pathologists, who should perform extensive molecular analysis of surgical non-GIST specimens in resected patients, and for oncologists, who should continue to follow up GIST patients.

Adjuvant radiotherapy for Merkel cell carcinoma: A systematic review and meta-analysis.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy with a high propensity for local recurrence and regional and distant metastases. The main treatment is surgery with narrow excision margins and draining nodes, plus or minus adjuvant radiotherapy (RT) on the surgical bed and/or lymph nodes. We performed a systematic review and meta-analysis of the benefits of adjuvant RT in MCC treatment. PubMed, EMBASE, and the Cochrane Library were systematically searched to identify relevant studies published before September 2018. Prospective trials and retrospective series comparing adjuvant RT vs. no RT in resected primary MCCs were included. Primary endpoint was to evaluate the outcomes of MCC patients who received adjuvant RT in term of overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) for OS and DFS were aggregated according to a fixed or random effect model. Secondary endpoints were local, locoregional, and distant DFS. A total of 17,179 MCCs across 29 studies were analysed. There was a significant difference in OS between the RT and no RT arms (HR = 0.81, 95%CI 0.75-0.86, P < 0.001). There was also a significant difference in DFS in favour of adjuvant RT (HR = 0.45, 95%CI 0.32-0.62, P < 0.001). Adjuvant RT improved locoregional DFS and local DFS but not distant DFS (HR = 0.3, 95%CI 0.22-0.42; HR = 0.21, 95%CI 0.14-0.33, and HR = 0.79, 95%CI 0.49-1.14, respectively). Meta-regression analysis showed that high Newcastle-Ottawa scale scores, stage I-II MCCs, shorter follow-up durations, size >2 cm, and being of a younger age were associated with increased OS. This systematic review and meta-analysis suggests a survival and DFS benefit for postoperative radiation of MCCs. Intermediate stage MCCs derive the maximum benefit with local and regional relapses reduced by 80% and 70%, respectively. Conversely, distant metastases were not significantly prevented.

Natural history, diagnosis, treatment and outcome of thyroid microcarcinoma (TMC) A mono-institutional 5 year experience.

Thyroid microcarcinoma (TMC) it's a rare type of differentiated thyroid cancer, which according to the World Health Organization measures 10 mm or less. Accounting 7-16 % of all thyroid carcinomas, it occurs at any age, more frequently in men, with a female to male ratio of 1:3. More frequently histotype is the papillary subset, PTCM. Aim of this study is to retrospectively evaluate the patients diagnosed with TMC in terms of their clinical and histopathological features. In our institution we collected 23 cases of TMC sampled on 338 plongeant being operated. All the tumors, in our study, were found incidentally during the treatment of benign thyroid diseases. All the sample were analyzed and prepared using the same frozen section technique. Surgical pathology identified 11 papillary microcarcinomas, 10 follicular microcarinomas, 1 oncocytary microcarcinomas and in 1 patient was found only a focal tireocitary transformation. TMC's prognosis and treatment is still a subject of controversy We propose our approch consisting in total thyroidectomy (less than 5 gr residual thyroid tissue), being considered the low rate of post-operative complications, and recurrences: all patients are disease-free at the median follow-up of 78 months (range 96 to 30 months). We have considered either the less malignancy habit of this neoplasia either its well prognosis.

Is primary surgery for locally advanced/metastatic breast cancer a better choice than chemotherapic treatment?

INTRODUCTION: A part of the literature supports the undoubtful advantage of neoadjuvant chemotherapy on the overall survival and for the possibility of surgical conservative treatment in locally advanced tumours after downstaging. Other authors report that primitive tumour's surgical removal at first, improves survival in cases with locally advanced /metastatic disease. The advantages were improvement of patient's health status, removal of a reservoir of neoplastic cell neoangiogenic cytokines and growth factors,and cytoreduction. MATERIALS AND METHODS: Aim of this study is to evaluate the effectiveness on the survival of a primary surgical treatment of the locally advanced tumours comparing two homogeneous groups. In the first group (GROUP 1) 40 patients were enrolled with stage III A, III B,IV tumours and were treated with primary surgery. The second group (GROUP 2) was made up of 40 patients with similar stage treated with neoadjuvant chemotherapy. The surgical treatment had the intention to remove the entire primary tumour. RESULTS: After a median follow up of 48,2 months,22,5 % of GROUP 1 died and 30 % of GROUP 2. The average survival of patients in GROUP 1 was 27,1 months while in GROUP 2 there was an average survival of 16,8 months. CONCLUSION: In conclusion surgical treatment plays a key role in the treatment of advanced/metastatic disease and is an independent factor associated with survival.

Successful use of rFVIIa for major breast surgery prophylaxis in congenital factor VII deficiency: a case report.

INTRODUCTION: Factor VII deficiency is a rare cause of haemorrhagic syndrome. The Authors describe a case of a 46 years old patient with congenital factor VII deficiency that successfully underwent breast surgery after treatment with Novoseven® before the procedure. MATERIALS AND METHODS: The AA used the schedule reported below to value the levels of PT and aPTT in the patient. Blood Collection: Venous blood from patient and control was collected in glass tubes for routine serum preparation and into plastic tubes (0.129 M sodium citrate, Becton-Dickinson Vacutainer Systems) in a ratio of blood to anticoagulant of 9:1. Platelet Poor Plasma (PPP) was obtained by centrifugation at 4.000 x g for 15 minutes at room temperature. The plasma was recentrifuged for another 10 min at 12000 g to fully eliminate platelet concentration. A normal control plasma pool was prepared by mixing equal volumes of platelet-free plasma obtained from at least 50 normal volunteers. Prothrombin time (PT) was measured with Recombiplastin (IL, Milano Italy). Activated partial thromboplastin times (APTT) was measured with APTT-SP (IL, Milano Italy). They were performed on the coagulation analyzer ACL 1000 (IL, Milano Italy). RESULTS: The results were interpreted from the ratio of the patient times to the normal control times (Table I). CONCLUSION: The infusion of Novoseven solved the clotting problems enabling the surgical procedure, without risks for the patient.

Successful use of rFVIIa for major breast surgery prophylaxis in congenital factor VII deficiency.

INTRODUCTION: Factor VII deficiency is a rare cause of haemorrhagic syndrome. The Authors describe a case of a 46 years old patient with congenital factor VII deficiency that successfully underwent breast surgery after treatment with Novoseven® before the procedure. MATERIALS AND METHODS: The AA used the schedule reported below to value the levels of PT and aPTT in the patient. Blood Collection: Venous blood from patient and control was collected in glass tubes for routine serum preparation and into plastic tubes (0.129 M sodium citrate, Becton-Dickinson Vacutainer Systems) in a ratio of blood to anticoagulant of 9:1. Platelet Poor Plasma (PPP) was obtained by centrifugation at 4.000 x g for 15 minutes at room temperature. The plasma was recentrifuged for another 10 min at 12000 g to fully eliminate platelet concentration. A normal control plasma pool was prepared by mixing equal volumes of platelet-free plasma obtained from at least 50 normal volunteers. Prothrombin time (PT) was measured with Recombiplastin (IL, Milano Italy). Activated partial thromboplastin times (APTT) was measured with APTT-SP (IL, Milano Italy). They were performed on the coagulation analyzer ACL 1000 (IL, Milano Italy). RESULTS: The results were interpreted from the ratio of the patient times to the normal control times (Table I). CONCLUSION: The infusion of Novoseven solved the clotting problems enabling the surgical procedure, without risks for the patient. KEY WORDS: Breast cancer, Factor VII deficiency, Major surgery, Recombinant fVIIa.

Laparoscopic treatment of celiac axis compression syndrome (CACS) and hiatal hernia: Case report with bleeding complications and review.

INTRODUCTION: Median arcuate ligament (MAL) malposition is a rare cause of celiac axis compression syndrome (CACS) or Dunbar syndrome. PRESENTATION OF CASE: A 26-year-old female presented with severe postprandial epigastric pain, weight loss, heartburn and regurgitation unresponsive to medical therapy. CT angiography and duplex ultrasound demonstrated the MAL crossing anterior to the celiac artery (CA). Reconstructions demonstrated CA compression, while the superior mesenteric artery (SMA) was normal. The MAL was laparoscopically divided, releasing the celiac axis. A concomitant Nissen fundoplication was performed. At 3-months follow-up, the CT-scan demonstrated no evidence of CACS with complete symptom resolution. DISCUSSION: Dunbar's syndrome can be treated with endovascular surgery, laparoscopic MAL division or vascular surgery.Six anatomical and morphologic variations of aortic and esophageal hiatus are described. The result of the analysis of these anatomical data leads to the conclusion that hiatus hernia, Dunbar's syndrome and GERD have a common etiopathogenesis and physiopathology. CONCLUSION: Laparoscopic treatment is useful and feasible in centers with experience in majorlaparoscopic surgery with reduced invasiveness, better cosmetic effect and shorter postoperative course.

Reconstruction with cutaneous flap after resection for breast cancer's skin metastases in a chemoresistant patient.

We reported a case of a breast cancer's skin metastases in a patient that had sustained 3 lines of chemotherapy. At first she received surgical treatment with Madden's mastectomy with dissection of axillary limphnodes and positioning of an expander. After that she underwent to chemo- and radiotherapy. The schedules we performed were: FEC, TC,Vinorelbine and Capecitabine. Only after the FEC there was a clinical remission just for 1 year. After that she underwent to surgery for the removal of a lozenge of skin on the right hemithorax, including also the subcutaneous tissue, a strip of muscular tissue, and a residue of the breast implant. The histology showed a multiple-nodules infiltration involving the dermis, the hypodermis, and the muscle. This pattern was valuated as a G3 breast cancer recurrence with ER 70%, PgR<5%, Ki67 50% Her2neu-. During the second line chemotherapy with TC she developed an high grade LCIS with lymphovascular infiltration on the left breast; on the right hemithorax there were cutaneous metastases with dermis' infiltration. Surgery with local excision was performed, and a cutaneous flap was realized.

Cat scratch disease presenting as breast cancer: a report of an unusual case.

Benign lymphoreticulosis (cat scratch disease, CSD) may have a clinical course that varies from the most common lymphadenitis localized in the site of inoculation, preceded by the typical "primary lesion," to a context of severe systemic involvement. Among these uncommon clinical aspects, there is mammarian granulomatous lymphadenitis which may appear as a mastitis or a solitary intraparenchymal mass, giving the impression of a breast tumor. In these cases, intensive clinical, instrumental, and laboratory investigations are necessary to exclude malignancy. Because of its rarity, in equivocal cases, it is reasonable to use surgical excision for accurate histological examination. We report a case of CSD of the breast in a 59-year-old woman, analyzing the clinical, histopathological, and instrumental appearance and also performing a literature review.