Sequential treatment with epirubicin, oxaliplatin and 5FU (EOF) followed by docetaxel, oxaliplatin and 5FU (DOF) in patients with advanced gastric or gastroesophageal cancer: a single-institution experience.

PURPOSE: The aim of this study was to evaluate the activity and safety of epirubicin (EPI), oxaliplatin (l-OHP) and 5fluorouracil (5FU) (EOF) followed by docetaxel (D), l-OHP and 5FU (DOF) in patients with advanced gastric or gastroesophageal junction (GEJ) cancer. METHODS: Forty-five patients were enrolled: 26 gastric and 19 GEJ cancer. Median age was 69 years (range 34-83); ECOG performance status was 0-1 in 37 patients. Treatment consisted of EPI 50 mg/m(2) combined with l-OHP 130 mg/m(2) on day 1 and continuous infusion 5FU 750 mg/m(2) days 1-5 (EOF), every 3 weeks for a maximum of 4 cycles. After EOF completion, patients received D 70 mg/m(2) combined with l-OHP 130 mg/m(2) on day 1 and continuous infusion 5FU 750 mg/m(2) days 1-5 (DOF), every 3 weeks for a maximum of 4 cycles. RESULTS: After sequential EOF/DOF, the overall response rate was 51.1 % (95 % CI 35.7-66.2 %) and 93.3 % of patients were progression free 6 months after the onset of chemotherapy. The median progression-free survival was 9.5 months (95 % CI 8.0-11.9 months), and the median overall survival was 15.8 months (95 % CI 13.6-18.9 months). Grade 3 neutropenia was observed in 15 patients (33.3 %) after sequential EOF/DOF. CONCLUSIONS: The sequential treatment EOF/DOF is feasible in well-selected patients with advanced gastric or GEJ cancer and shows encouraging survival results.

Rechallenge of docetaxel combined with epirubicin given on a weekly schedule in advanced castration-resistant prostate cancer patients previously exposed to docetaxel and abiraterone acetate: a single-institution experience.

The aim of this paper was to evaluate the activity and tolerability of weekly docetaxel (D) combined with weekly epirubicin (EPI) in patients with advanced castrate-resistant prostate cancer (CRPC) previously exposed to D and abiraterone acetate (AA). Locally advanced or metastatic CRPC patients with 0-2 performance status, who had progressed after D and AA therapy, were included in the study. Previous treatment with chemotherapy agent cabazitaxel was also admitted. Treatment consisted of D 30 mg/m(2) intravenously (i.v.) and EPI 30 mg/m(2) i.v., every week (D/EPI). Chemotherapy was administered until disease progression or unacceptable toxicity. In our institution, twenty-six patients received D/EPI: their median age was 72 years (range 59-83 years). Twenty-three (88.5%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in seven patients (26.9%, 95% CI: 0.11-0.47); of these, five had achieved a ≥50% PSA response during prior first-line D and six had achieved a PSA response during prior AA Among the subjects who were symptomatic at baseline, pain was reduced in nine patients (38.1%) with a significant decrease in analgesic use. Median progression-free survival was 4.4 months (95% CI, 3-5.2), and median overall survival was 10.7 months (95% CI, 8.9-18.4). Treatment was well tolerated and no grade 4 toxicities were observed. Our findings suggest that weekly D/EPI is feasible and active in heavily pretreated advanced CRPC patients and seem to support the hypothesis that the addition of EPI to D may lead to overcome the resistance to D in a subgroup of patients.

Deregulation of DNA-dependent protein kinase catalytic subunit contributes to human hepatocarcinogenesis development and has a putative prognostic value.

BACKGROUND: The DNA-repair gene DNA-dependent kinase catalytic subunit (DNA-PKcs) favours or inhibits carcinogenesis, depending on the cancer type. Its role in human hepatocellular carcinoma (HCC) is unknown. METHODS: DNA-dependent protein kinase catalytic subunit, H2A histone family member X (H2AFX) and heat shock transcription factor-1 (HSF1) levels were assessed by immunohistochemistry and/or immunoblotting and qRT-PCR in a collection of human HCC. Rates of proliferation, apoptosis, microvessel density and genomic instability were also determined. Heat shock factor-1 cDNA or DNA-PKcs-specific siRNA were used to explore the role of both genes in HCC. Activator protein 1 (AP-1) binding to DNA-PKcs promoter was evaluated by chromatin immunoprecipitation. Kaplan-Meier curves and multivariate Cox model were used to study the impact on clinical outcome. RESULTS: Total and phosphorylated DNA-PKcs and H2AFX were upregulated in HCC. Activated DNA-PKcs positively correlated with HCC proliferation, genomic instability and microvessel density, and negatively with apoptosis and patient's survival. Proliferation decline and massive apoptosis followed DNA-PKcs silencing in HCC cell lines. Total and phosphorylated HSF1 protein, mRNA and activity were upregulated in HCC. Mechanistically, we demonstrated that HSF1 induces DNA-PKcs upregulation through the activation of the MAPK/JNK/AP-1 axis. CONCLUSION: DNA-dependent protein kinase catalytic subunit transduces HSF1 effects in HCC cells, and might represent a novel target and prognostic factor in human HCC.

[Colorectal carcinoma in the young. Prognostic factors]. / Il carcinoma colo-rettale nel giovane. Fattori prognostici.

Colorectal carcinoma is the third most frequently diagnosed malignant neoplasm. Usually patients affected by this neoplasia belong to VI decade of life. However approximately 2-8% of tumors arise in patients with age under 40 years. Aim of the study was to analyse the results of surgical treatment of colorectal cancer in patients aged under forty. From January 1987 to December 2002, 46 patients under forty years with colorectal cancer underwent surgical procedure. No perioperative mortality was registered, and complications were evidenced in nine patients (20%). Actuarial five years survival was 33%, and overall mean survival was 53 months. Univariate and multivariate analyses identified as prognostic factors the tumor grade, Dukes' stage, nodal status, and length of symptoms.

[Primary adenocarcinoma of the ureter. Case report]. / Adenocarcinoma primitivo dell'uretere: caso clinico.

Primary ureteral adenocarcinoma is an infrequent histological type of urinary neoplasm. Many authors consider intestinal metaplasia the pivotal event of the pathogenetic process, whether it occurs on a pre-existing urothelial carcinoma or on a normal urothelium. Diagnosis is essentially based on case history and clinical findings (hematuria and pain) and on diagnostic imaging. Treatment is surgical and the ideal procedure is nephroureterectomy with excision of a bladder margin adjacent to the ureteral opening and ispilateral para-aortoiliac lymphadenectomy. A 76-year-old man with primary adenocarcinoma of the ureter case is reported.

Clinical significance of serum gastrin levels in patients with colorectal cancer.

AIMS: An association between elevated serum gastrin levels and the presence of human colorectal cancer has been reported, and gastrin has been shown to stimulate the growth of experimentally induced colon neoplasia. The aim of this study was to determine the preoperative and postoperative concentrations of serum gastrin in 53 patients with colorectal cancer and to assess the correlation between gastrin levels and tumor characteristics and prognosis. MATERIALS AND METHODS: A prospective study was performed over a six-year period during which 53 patients received potentially curative surgery for colorectal cancer. The prognostic variables used for the analysis included age, sex, tumor site, stage and degree of differentiation, preoperative and postoperative serum values of carcinoembryonic antigen (CEA) and gastrin, cancer-related mortality, and survival. CEA and gastrin serum values were determined using radioimmunological methods. Follow-up was carried out with clinical and radiological tests. RESULTS: The mean preoperative gastrin concentration was 51.2+/-27.4 pg/mL (range 12-146). Significantly increased serum gastrin concentrations, which returned to normal after surgery, were detected only in patients with well-differentiated cancer (74.2+/-28.3 pg/mL; moderately differentiated, 52.1+/-23.8; poorly differentiated, 29.9+/-12.3, p=0.02). The prognosis was unrelated to serum gastrin level; instead, tumor stage, preoperative CEA value, and degree of differentiation affected patient survival. CONCLUSIONS: This study showed that the serum gastrin concentration is not an appropriate clinical oncogenic factor. Although occurring only in well-differentiated tumors, serum gastrin is unrelated to the prognosis of patients with colorectal cancer.

[Rectal cancer in women]. / Il cancro del retto nella donna.

A retrospective chart review was performed utilizing the First Department of Surgery of the University of Rome "La Sapienza" Medical School database. Ninety-two women who underwent abdominal surgery between 1980 and 1993 for rectal cancer were identified. Data collected included demographics, history, intraoperative findings and complications, cancer histology and stage and follow up. Special attention was focused on intraoperative incidental gynecological findings and follow up. Twenty-two patients being previously submitted to hysterectomy and three with oral intake of hormones were dismitted from the study. Of the remaining 67 patients gynecological procedure was associated to rectal surgery because of a previously undiagnosed gynecological condition. No prophylactic oophorectomies were performed. At follow up 7 patients experienced further surgery for gynecologic disease. The necessity to offer these patients the benefit of a preoperative informed decision about adjunctive gynecologic surgery and indications for bilateral oophorectomy is discussed.

Type B1 thymoma in multiple endocrine neoplasia type 1 (MEN-1) syndrome.

AIMS AND BACKGROUND: Multiple endocrine neoplasia (MEN) syndromes include a group of disorders characterized by the neoplastic transformation of two or more endocrine tissues. In type 1 syndrome (MEN-1), pituitary, parathyroid and pancreatic islet tumors are most frequently represented. Thymic neoplasms are also rarely associated, and thymectomy during subtotal or total parathyroidectomy should always be considered. STUDY DESIGN: The authors describe a rare case of a 22-year-old male who presented a type B1 thymoma without myasthenia gravis associated to hyperparathyroidism, corticoadrenal adenoma and three neuroendocrine pancreatic lesions (somatostatinoma, glucagonoma and insulinoma).

[A case of carcinoid with multiple sites in the jejunum and distal ileum]. / Un caso di carcinoide a localizzazioni multiple su digiuno ed ileo distale.

Multiple carcinoid tumors of the small bowel with more than 3 lesions are very unusual. The authors report a case with 4 lesions, 2 of those localized in the jejunum with more advanced infiltration of the wall and extension to regional mesenteric lymph nodes, revealed by ultrasonography. The relative low incidence and particularly the vague, nonspecific clinical presentation, the unusual site in the jejunum, and failure of the radiological examine of one year before lead to not suspect this condition prior to US examination. However, the feature of asymmetric, concentric thickening of the bowel wall requiring a more accurate exam by CT with oral contrast was able to confirm the suspect of the intestinal tumor. The patient, 80 year old, underwent radical surgery with a wide lymph nodes dissection as well as double resection of the jejunum and distal ileum. The post-surgical outcome was uneventful. A 12-month follow-up is free of the disease.

Recurrent intussusception of the sigmoid colon caused by a transanal protruding sessile tubulo-villous malignant polyp.

We report a case of a 35 year-old woman with a large malignant sessile tubulo-villous polyp of the proximal end of a dolico-sigmoid colon causing intussusception and transanal prolapsing. The diagnosis presented some difficulties being the intussusception intermittent. The clinical feature had been initially misdiagnosed for a very large bleeding polyp (5 cm in size), protruding out of the anus with a long pedicle in the rectum. The histology of multiple bioptic samples of the lesion revealed malignancy. Conventional radiologic studies (plain x-rays, barium enema) after metal clips had been placed on the head of the polyp before it rose up the colon, led to the correct diagnosis without, nevertheless, documenting intussusception. An elective surgical resection of the dolico-sigmoid colon allowed the correct diagnosis and the curative treatment of the colonic intussusception and the malignancy.

Clinical behavior of solitary fibrous tumors of the pleura. An immunohistochemical study.

Localized fibrous tumors of the pleura are uncommon, generally asymptomatic and usually have a benign behavior even if in a few cases a malignant variant can be observed. We report 11 cases of localized pleural neoplasms submitted to surgical resection during the period 1987-1996. The differentiation between the localized fibrous as well as the less frequent localized malignant mesothelioma has been researched employing cyto-histopathologic and immunohistochemical assays. For the purpose of identifying solitary fibrous tumors of pleura that will behave in malignant manner, we applied the more recent criteria of specific immunohistochemical stains, microvessel density and proliferation mdex. All solitary fibrous tumors resulted positive for Vimentin and negative for Cytokeratin. Among these forms, high cellularity and microvessel density, high expression of Ki 67 and CD31 and negativity of CD34 prognostic factors for a poor prognosis.

[Transpyloric prolapse of a gastric carcinoma arising from a pedunculated hyperplastic polyp]. / Prolasso transpilorico di carcinoma gastrico insorto su polipo iperplastico peduncolato.

A case of gastric carcinoma developed on a large pedunculated hyperplastic polyp prolapsed into duodenum is reported. The cases of transpyloric prolapsed primary pedunculated gastric carcinoma are rare, only 34 cases have been described in Japan during the past 35 years, including the sessile forms. These gastric polyps should be considered in the differential diagnosis of intraluminar filling defects of the duodenal bulb. Endoscopy and biopsy are essential for a correct diagnostic evaluation. Large hyperplastic polyps, especially if prolapsed, require a surgical excision.

Early stage human colorectal cancer: prognostic value of nm23-H1 protein overexpression.

Nm23 gene codifies for a nucleoside diphosphate kinase allowing the intracellular transduction of the signals. In colorectal cancer nm23 protein expression seems related to the progression of the disease. By immunohistochemistry we have studied the intracytoplasmatic nm23 H1 protein expression in 20 patients affected by colorectal cancer at initial stage. In 12 cases it resulted elevated and in four the disease recurred. The overexpression was not correlated with other prognostic factors. Nm23 H1-positive patients affected by colorectal cancer at initial stage could be considered at risk for disease recurrence and included in a more frequent follow-up protocol.

Low rectal cancer--what is the choice?

In patients operated on for low rectal cancer, the functional results, disease recurrence, and survival have been evaluated with respect to the type of surgery performed. Particular attention was paid to analysis of the pathologic aspects, considered in our opinion, as risk factors for recurrence. The investigation was carried out on 131 patients, of whom 70 received anterior resection, 55 abdominoperineal resection, and 6 local treatment. Abdominoperineal resection was carried out in more advanced disease. Postoperative mortality was 2.1 percent after anterior resection and 0 after abdominoperineal resection or local treatment. Follow-up, carried out in 96 patients (44 anterior resections, 46 abdominoperineal resections, and 6 local treatments), ranged from 12 to 84 (mean, 33.3) months. Recurrence rate was 53.3 percent after abdominoperineal resection and 28.9 percent after anterior resection. Recurrence appears not be related to the treatment performed, but rather depend on certain aspects of the neoplasm such as diameter exceeding 5 cm, extraparietal infiltration, lymphangitis, and tumor indifferentiation. We observed anastomotic recurrence in 28.6 percent of patients with a margin of less than 2 cm. An intensive follow-up scheme enabled us to recognize this type of recurrence early and to reoperate with radical intent. One year after anterior resection functional results were encouraging. No severe incontinence was reported. Local treatment was performed in carefully selected patients (T1, N0) and no cases of mortality or recurrence were observed.

Tissue CEA as prognostic indicator in a series of 31 cases of gastric cancer.

The role of tissue CEA localization as a complementary factor in prognosis of patients affected by gastric cancer is analyzed. In a group of 31 gastric tumors, tissue CEA was always present in the apical portion of the tumor cell cytoplasm and in the glandular lumen, while in 23 cases it was found in the stroma, and in superficial and deep cell cytoplasm in 26 and 20 cases respectively. The serum marker levels were over 3 ng/ml in 19 patients. A relationship between CEA localization and tumor stage was observed. The more the tumors were advanced, the more the marker was found in the stroma and in the cytoplasm of superficial and deep cells. The same was found for CEA localization and serum CEA levels. The opposite trend was evidenced for the degree of tumor differentiation. In well differentiated tumors in a high percentage of cases the marker was present in the stroma and in the cytoplasm of superficial and deep cells as compared with undifferentiated tumors. No relationship between the histologic type and CEA localization was found.

[Significance of biliary lithiasic pathology in the etiopathogenesis of carcinoma of the large intestine]. / Significato della patologia litiasica biliare nella etiopatogenesi del carcinoma del grosso intestino.

With the purpose to study the eventual existence of a correlation between biliary lithiasis and colon-rectum carcinoma, the authors effected a retrospective study of the clinical material concerning 1283 patients hospitalized in the 1st Surgery Institute for large intestine carcinoma. The relative anamnestic data were compared with those of a control population. The results emerging from the research, checked in their statistic significance, seem to support the existence of such correlation. The hypothesis of a possible common etiopathogenesis of both diseases is proposed.