Surgical management of rectal GIST. A case report and a review of literature.

AIM: Rectal GIST is a rare tumor of the gastrointestinal tract. The few literature cases didn't show significant evidence about diagnostic and therapeutic management. We present a rare case of rectal GIST treated with laparoscopic anterior rectal resection (RARLs) preceded by neoadjuvant therapy with Imatinib Mesylate (IM). CASE REPORT: A 68-year-old woman with abdominal pain, rectal bleeding and palpable mass on rectal exam has been subjected to computerized tomography (CT) of the abdomen and pelvis and magnetic resonance imaging (MRI) that revealed a rectal GIST of 5x4x2 cm at 3 cm from anal verge. The diagnosis was confirmed with colonoscopy. After 3- mounts neoadjuvant therapy with IM, which allowed to down-stage the neoformation, the patient underwent RARLs without intraoperative or postoperative complications. Immunohistochemistry revealed cluster of differentiation CD 117 positive, HPF 5/50, Ki 67overexpressed. PDGF mutation was detected. The patient was therefore taken in charge by the oncologist. DISCUSSION AND CONCLUSION: Resection appear curative for rectal GIST. Extensive resections aren't necessary because of downstaging after IM therapy. However, the appropriate surgical technique is still debated. Further studies are necessary for a correct surgical standardization. KEY WORDS: Rectal GIST, Cajal cell, Laparoscopic rectal resection, Imatinib.

Primary malignant melanoma of the bowel diagnosed following a bowel intussusception in an adult patient. A case report and review of the literatureport.

AIM: Primary small bowel melanoma is a very rare clinical entity with a paucity of publications in literature. Most cases of gastrointestinal melanomas are metastatic lesions arising generally from primary lesion of the skin, eyes, or anus. We present a case of a small bowel intussusception with primary malignant melanoma as lead point and a gluteal melanoma metastasis after four years free from disease. CASE REPORT: A 77-year-old female has come to our attention with signs and symptoms of intestinal occlusion. She was subjected to a computerized tomography (CT) of the abdomen and pelvis that revealed small bowel intussusception caused by intestinal polypoid lesion. She was treated with a bowel resection. The histological exam has shown the presence of an amelanocytic malignant melanoma. The examination of skin, eyes, esophagus, colon and anus, a tot al body contrast- enhanced CT and a bone scintigraphy were negative for primary melanoma. So, the final diagnosis was primary melanoma of the ileum. After four-years disease-free survival, the patient came back to our attention for a gluteal melanoma metastasis, that was surgically removed. Afterwards she started immunotherapy, that is still ongoing. DISCUSSION AND CONCLUSION: The diagnosis and the treatment of primary intestinal melanoma is a challenging due to the lack of scientific indications. Our case shows how an early diagnosis, although accidental, can offer a good survival free from disease. Moreover, a careful follow-up of our patients allows us to promptly identify neoplasm recurrence or distant metastasis that can be treated with surgery and systematic therapy. KEY WORDS: Intussusception, Primary bowel melanoma.

Endoscopic Ultrasound-Guided Fine Needle Aspiration of a PET/CT-Positive Small Hilar Lymph Node for the Diagnosis of Metastatic Merkel Cell Carcinoma.

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Weekly alternate intensive regimen FIrB/FOx in metastatic colorectal cancer patients: an update from clinical practice.

BACKGROUND: Several trials evaluated the role of intensive regimens, made of triplet chemotherapies plus bevacizumab, as first-line treatment for patients with metastatic colorectal cancer (mCRC). We previously reported, in a Phase II prospective study, the efficacy and the tolerability of FIrB/FOx regimen, reporting interesting results in terms of received dose intensities (rDIs) and safety. METHODS: We reported a retrospective update of 85 patients treated with FIrB/FOx, an intensive regimen of 5-fluorouracil, bevacizumab, and weekly alternate irinotecan and oxaliplatin, to confirm its feasibility in "real life". Subgroup analyses were performed, particularly among patients treated with standard and modified FIrB/FOx (based on age, performance status, and/or comorbidities). RESULTS: Overall, 3-month objective response rate (ORR) and 6-month ORR were 75.9% and 55.3%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 14.4 and 34.9 months, respectively. Among the patients treated with standard and modified regimens, 3-month ORR, PFS, and OS were 75.8% and 76% (P=1.0000), 14.4 and 14.4 months (P=0.8589), and 37.8 and 26.6 months (P=0.7746), respectively. Among the K/NRAS wild-type and K/NRAS mutant patients, 3-month ORR, PFS, and OS were 95.2% and 74.5% (P=0.0526), 15.3 and 14.4 months (P=0.8753), and 37.8 and 51.4 months (P=0.8527), respectively. The rDIs were ≥80% of full doses both in the standard and in the modified regimens subgroups. Cumulative G3/4 toxicities were neutropenia (14.1%), diarrhea (17.6%), asthenia (9.4%), vomiting (5.6%), and hypertension (16.5%). CONCLUSION: This update shows that intensive regimens such as FIrB/FOx are also feasible options for first-line treatment of mCRC patients in the "real-life" setting.

Timed­flat infusion of 5­fluorouracil with docetaxel and oxaliplatin as first­line treatment of gastroesophageal adenocarcinoma: A single institution experience with the FD/FOx regimen.

To date, there is no consensus regarding first­line chemotherapy for patients with HER2­negative, locally advanced/metastatic gastric cancer (a/m GC). In the present study we reported a retrospective case­series of patients treated with a weekly regimen containing timed­flat infusion of 5­fluorouracil (TFI/5­FU), docetaxel and oxaliplatin. From June 2007 to July 2017, 32 consecutive a/m GC patients were treated with first­line standard (st) or modulated (mod) 'FD/FOx' regimen: Weekly 12 h (from 10.00 p.m. to 10.00 a.m.) TFI/5­FU for two consecutive nights at 900 mg/m2/day, associated to weekly alternating docetaxel, 50 mg/m2 and oxaliplatin, 80 mg/m2. The median age of the patients was 60 years and their Eastern Cooperative Oncology Group­performance status (ECOG­PS) was as follows: i) ECOG­PS 0/1, (n=28, 87.5%); and ii) ECOG­PS 2 (n=4, 12.5%). Patient activity, efficacy and safety data were collected and subgroup analyses were conducted among patients treated with st and mod FD/FOx. In the intention­to­treat (ITT) analysis, the objective response rate (ORR) was 75% (95% CI, 53­90) and the disease control rate (DCR) was 87.5% (95% CI, 67.6­97.3). After a median follow­up of 16 months, median progression­free survival (PFS) and median overall survival (OS) were 14.0 and 19.0 months, respectively. The received dose­intensities were ~80% of the standard doses for each agent. The most relevant treatment­related grade 3 adverse events were: Neutropenia (40.6%), asthenia (18.7%) and diarrhea (18.7%). The only treatment­related grade 4 adverse event was neutropenia (9.3%). No febrile neutropenia was observed and none of the patients died as a result of adverse events. FD/FOx regimen appeared to be a feasible option as a first­line treatment of a/m GC patients, especially in case of high­tumor burden, with the need of rapid tumor shrinkage and disease­related symptoms palliation.

Dose-finding study of oxaliplatin associated to capecitabine-based preoperative chemoradiotherapy in locally advanced rectal cancer.

INTRODUCTION: Proper administration timing, dose-intensity, efficacy/toxicity ratio of oxaliplatin added to fluoropyrimidin should be improved to safely perform two-drugs intensive preoperative chemoradiotherapy in locally advanced rectal cancer (LARC). This dose-finding study investigated recommended oxaliplatin dose, safety of oxaliplatin/capecitabine regimen and preliminary activity. METHODS: Schedule: oxaliplatin dose-levels, 35-40 mg/m2/week; capecitabine 825 mg/m2/ twice daily, radiotherapy on rectum/nodes, 50/45 Gy, 45 and 9 boost/45 Gy, in first 5 and subsequent patients, 5 days/week, respectively; for 5 weeks. Pathologic complete response (pCR) 10% was projected in order to positively affect clinical outcome. RESULTS: Seventeen fit <75 years patients enrolled: median age 60; young-elderly 4 (23%); T3/T4, 15/2, N0/N1/N2, 7/9/1. At first dose-level, no dose-limiting toxicity (DLT). At second, 2 DLT, G3 mucositis, G3 thrombocytopenia, in 2/6 patients (33%). Oxaliplatin recommended dose, 40 mg/m2/week. Cumulative G3-4 toxicities: mucositis 6%, thrombocytopenia 6%. Limiting toxicity syndromes 18%, 25% in young-elderly, all single site. Objective response rate intent-to-treat 94%. Sphinter preservation 87%, pCR 6%. After 17 months follow-up, progression-free survival and overall survival were not reached. CONCLUSIONS: Oxaliplatin can be safely added to preoperative capecitabine-based chemoradiotherapy at the recommended dose 40 mg/m2/week, in LARC, with promising pCR and high activity.

Unilateral paravertebral block compared with subarachnoid anesthesia for the management of postoperative pain syndrome after inguinal herniorrhaphy: a randomized controlled clinical trial.

Inguinal herniorrhaphy is a common surgical procedure. The aim of this investigation was to determine whether unilateral paravertebral block could provide better control of postoperative pain syndrome compared with unilateral subarachnoid block (SAB). A randomized controlled study was conducted using 50 patients with unilateral inguinal hernias. The patients were randomized to receive either paravertebral block (S group) or SAB (C group). Paravertebral block was performed by injecting a total of 20 mL of 0.5% levobupivacaine from T9 to T12 under ultrasound guidance, whereas SAB was performed by injecting 13 mg of 0.5% levobupivacaine at the L3 to L4 level. Data regarding anesthesia, hemodynamic changes, side effects, time spent in the postanesthesia care unit, the Karnofsky Performance Status, acute pain and neuropathic disturbances were recorded. Paravertebral block provided good anesthesia of the inguinal region without patient or surgeon discomfort, with better hemodynamic stability and safety and with a reduced time to discharge from the postanesthesia care unit compared with SAB. During the postsurgical and posthospital discharge follow-ups, rest and incident pain and neuropathic positive phenomena were better controlled in the S group than in the C group. The consumption of painkillers was higher in the C group than in the S group throughout the follow-up period. Paravertebral block can be considered a viable alternative to common anesthetic procedures performed for inguinal hernia repair surgery. Paravertebral block provided good management of acute postoperative pain and limited neuropathic postoperative disturbances.

Differential prognosis of metastatic colorectal cancer patients post-progression to first-line triplet chemotherapy plus bevacizumab, FIr-B/FOx, according to second-line treatment and KRAS genotype.

Clinical outcome post-progression to first-line triplet chemotherapy (CT) plus bevacizumab (FIr-B/FOx) was evaluated in metastatic colorectal cancer (MCRC) patients (pts). Second-line treatment was selected according to fitness, KRAS genotype, previous efficacy and safety. Efficacy was evaluated and compared according to treatment or KRAS genotype, using log-rank analysis. Among 54 pts, median overall survival (OS) post-progression was 12 months, significantly better in 40 (74.1%) treated compared to 14 (25.9%) who died without further treatment. Second-line surgical treatment, 4 pts (7.4%), medical treatment, 36 pts (66.7%): triplet CT plus targeted agent, 10 (18.5%); triplet regimens, 19 (35.2%); doublet/monotherapy, 7 (13%). At follow-up of 14 months, objective response rate (ORR) was 38%, metastasectomies 12.5%, progression-free survival (PFS) 10 months, OS 14 months. According to treatment, ORR, metastasectomies, PFS and OS were significantly favourable in triplet CT plus targeted agent compared to triplet, respectively: 80%, 40%, 13 months, not reached; 28%, 6%, 8 months, 11 months. PFS and OS were significantly worse in c.35 G>A mutant compared to wild-type and/or other mutant patients. Prognosis after progression to first­line FIr-B/FOx may be significantly favourable in MCRC pts re-challenged with intensive regimens, and unfavourable in c.35 G>A KRAS mutant patients.

Prognostic relevance of KRAS genotype in metastatic colorectal cancer patients unfit for FIr-B/FOx intensive regimen.

First-line triplet chemotherapy plus bevacizumab (FIr-B/FOx) can improve efficacy of metastatic colorectal cancer (MCRC), KRAS wild-type and mutant. Prognostic relevance of KRAS genotype was evaluated in patients unfit for FIr-B/FOx, treated with conventional medical treatments. Consecutive MCRC patients not eligible for FIr-B/FOx regimen due to age (≥75 years) and/or comorbidities were treated with tailored conventional first-line treatments. KRAS codon 12/13 mutations were screened by direct sequencing. Activity and efficacy were evaluated and compared according to medical treatments, age (non-elderly and elderly≥65 years), comorbidity stage (Cumulative Illness Rating Scale), metastatic extension (liver-limited and other/multiple metastatic), and KRAS genotype, using log-rank. Selected first line treatments were medical in 37 patients (92.5%), and surgical in 3 patients (7.5%). Medical treatment regimens: triplet, 18 (45%); doublet, 15 (37.5%); mono-therapy, 4 (10%). At median follow-up of 8 months, objective response rate (ORR) was 37%, median progression-free survival (PFS) 7 months, liver metastasectomies 8% (liver-limited disease 37.5%), median overall survival (OS) 13 months. Triplet regimens failed to significantly affect clinical outcome, compared to doublet. According to KRAS genotype, ORR, PFS and OS were, respectively: wild-type 50%, 8 months, 13 months; mutant 25%, 6 months, 9 months. KRAS genotype wild-type compared to mutant significantly affected PFS, while not OS. KRAS c.35 G>A mutation (G12D) significantly affected worse PFS and OS compared to wild-type and/or other mutations. KRAS genotype, specifically the c.35 G>A KRAS mutation, may indicate poor prognosis in MCRC patients unfit for intensive medical treatments.

Multidisciplinary management of hepatocellular carcinoma in clinical practice.

BACKGROUND: Hepatocellular carcinoma (HCC) patients require different treatment strategies according to disease extension, liver function, and patient's fitness. We evaluated HCC multidisciplinary management in clinical practice. METHODS: Consecutive patients were followed and treated with tailored medical, locoregional, and surgical treatments, according to disease stage and patient's fitness (age, Cumulative Illness Rating Scale (CIRS)). Activity, efficacy, and safety were evaluated. RESULTS: Thirty-eight patients were evaluated: median age, 74; elderly 92%; CIRS secondary 28 (74%); Child-Pugh A 20 (53%), B 11 (29%); and Barcelona Clinic Liver Cancer (BCLC) 0 2 (5%), A 9 (24%), B 10 (26%), C 13 (34%), and D 4 (11%). Overall survival (OS) was 30 months. At 9 months median follow-up, among 25 unresectable HCC, OS was 10 months; BCLC B-D unfit for sorafenib showed OS 3 months. Ten patients (40%) received sorafenib: Child-Pugh A 5 (50%) and B 5 (50%) and disease control rate 89%, progression-free survival 7 months, and OS 9 months. G3-4 toxicities: anorexia, hypertransaminaemia, hyperbilirubinemia, and hypercreatininemia. Limiting toxicity syndromes were 40%, all multiple sites. CONCLUSION: HCC patients require multidisciplinary clinical management to properly select tailored treatments according to disease stage, fitness, and liver function. Patients suitable for sorafenib should be carefully selected, monitored for individual safety, and prevalently characterized by limiting toxicity syndromes multiple sites.

Effectiveness and safety of intensive triplet chemotherapy plus bevacizumab, FIr-B/FOx, in young-elderly metastatic colorectal cancer patients.

Four-drug regimens, such as FIr-B/FOx schedule, can improve efficacy of first-line treatment of metastatic colorectal cancer (MCRC) patients. The present study specifically evaluates feasibility of FIr-B/FOx first-line intensive regimen in fit young-elderly MCRC patients, representing approximately 40% of overall MCRC patients. Activity, efficacy, and safety were equivalent to overall MCRC patients, not significantly different according to KRAS genotype. Clinical outcome was significantly prolonged in liver-limited compared to other/multiple metastatic disease. Safety evaluation of the individual young-elderly patient showed that limiting toxicity syndromes (LTS) in multiple sites were significantly increased, compared to LTS in single site, with respect to non-elderly patients.

Effectiveness of liver metastasectomies in patients with metastatic colorectal cancer treated with FIr-B/FOx triplet chemotherapy plus bevacizumab.

BACKGROUND: Intensive medical treatment increases resection rate of liver metastases in patients with metastatic colorectal cancer (MCRC). The effectiveness of liver metastasectomies was evaluated in patients with MCRC who were treated with previously reported FIr-B/FOx (triplet chemotherapy plus bevacizumab). PATIENTS AND METHODS: Fifty patients with MCRC enrolled in the reported phase II study were classified according to involved metastatic sites (liver-only metastatic site, multiple metastatic sites) and the extent of liver metastases (single, multiple). Surgical resectability of liver metastases was evaluated at baseline and every 3 cycles of FIr-B/FOx treatment. The resection rate of liver metastases, activity, and efficacy were evaluated; progression-free survival (PFS) and overall survival (OS) were compared by using the log-rank test. RESULTS: Patients with liver MCRC were 33 of 50 consecutive unselected patients with MCRC: liver limited, 22 patients; multiple metastatic sites, 11 patients. Liver metastasectomies were performed in 13 patients: 26% of 50 patients with MCRC, 39% of 33 patients with liver MCRC. In patients with liver-only MCRC, a secondary liver surgery was performed in 54%: 6 of 9 single and 6 of 13 multiple liver metastases. Also, 1 liver and lung metastasectomy was performed. Pathologic complete responses were achieved in 2 patients (15%). The conversion rate of unresectable liver metastases was 83%. Objective response rate, PFS, OS were, respectively: 84%, 11 and 23 months in 33 liver MCRC; 86%, 17 and 44 months in 22 liver-limited patients. PFS and OS were significantly increased in patients with liver-limited metastases compared with multiple metastatic sites and single compared with multiple liver metastases. CONCLUSION: The FIr-B/FOx regimen may increase the resection rate of liver metastases and improve clinical outcome of patients with liver-only MCRC.