Sphincter preservation in four consecutive phase II studies of preoperative chemoradiation: analysis of 247 T3 rectal cancer patients.

AIMS AND BACKGROUND: To evaluate the impact of preoperative chemoradiation on sphincter preservation in patients with low-medium locally advanced resectable rectal cancer treated by four chemoradiation schedules. MATERIALS AND METHODS: Between 1990 and 2002, 247 patients were treated according to four schedules of chemoradiotherapy: FUMIR (5-fluorouracil, mitomycin, external beam radiotherapy 37.8 Gy), PLAFUR (cisplatinum, 5-fluorouracil, external beam radiotherapy 50.4 Gy),TOMRT (raltitrexed, external beam radiotherapy 50.4 Gy), and TOMOXRT (raltitrexed, oxaliplatin, external beam radiotherapy 50.4 Gy). Four to five weeks after chemoradiation, patients were restaged and surgery was performed 2-3 weeks later. RESULTS: Overall, the sphincter-saving surgery was performed in 82.5% of patients. In patients candidate to an abdominoperineal resection before chemoradiaton (distance tumor-anorectal ring, < 30 mm) a sphincter-saving surgery was possible in 58% of cases: 44% (FUMIR), 52% (PLAFUR), 63% (TOMRT), 76% (TOMOXRT) (P < 0.017). The involved surgeons kept the same surgical criteria in performing sphincter-saving surgery. After chemoradiation, patients with tumor location still between 0 and 30 mm received sphincter-saving surgery according to the protocols: 33% (FUMIR), 42% (PLAFUR), 50% (TOMRT), 64% (TOMOXRT) (P = 0.066). CONCLUSIONS: Even though the surgeons' skill in performing sphincter-saving surgery could be improved with time, the high rate of this procedure in the latest schedules suggests an impact of the new drugs in promoting tumor downsizing and therefore sphincter-saving surgery.

A giant papillary carcinoma of the breast treated with mastectomy and bipedicled TRAM flap.

Although the surgical treatment of breast cancer has become more conservative in the last decades, some patients still arrive at the first physical examination with advanced diseases and with large skin infiltration. We report an unusual case of giant invasive papillary carcinoma of the breast underwent mastectomy and reconstruction with a bipedicled transverse rectus abdominis myocutaneous (TRAM) flap.

[Maximum gastric cancer diameter: prognostic factor or important clinical feature?]. / Diametro massimo del tumore nel carcinoma gastrico. Fattore prognostico o rilevante parametro clinico?

Maximum tumor diameter (DMAX) is considered by many Authors as an im prognostic factor in gastric cancer (GC) correlated with tumor depth (pT). Aim of this retrospective study was to evaluate the prognostic value of DMAX and its predictive role of tumor stage in a series of 164 gastric cancer patients. One hundred and sixty-four patients underwent gastrectomy between January 1994 and December 2004. DMAX value was measured on resected specimens fixed in 10% formalin solution with cut-off of 40 mm. Tumors according to these measurements were classified in DMAX1 < or = mm and DMAX2 >40 mm. The prognostic significance of DMAX along with other factors was evaluated with log-rank test and Cox regression. The correlation between DMAX and other variables was calculated by Spearman test. Overall 5-year survival rate is 56.6%. DMAX resulted significantly linked to survival at univariate analysis (p = 0.0001). The Spearman correlation test showed that DMAX is strongly correlated with tumor stage (positive predictive value of 88.5%), pT, pN, residual of tumor and grading. Our results showed that patients with large tumor at an increased risk for tumor advancement and, therefore, DMAX could represent a useful parameter for selection of patients for neoadjuvant protocols.

Long-term results after neoadjuvant radiochemotherapy for locally advanced resectable extraperitoneal rectal cancer.

PURPOSE: This study was designed to evaluate long-term outcome in locally advanced resectable extraperitoneal rectal cancer treated by preoperative radiochemotherapy. METHODS: Eighty-three consecutive patients who developed locally advanced resectable extraperitoneal rectal cancer underwent preoperative concomitant radiochemotherapy followed by surgery, including total mesorectal excision. RESULTS: Median follow-up was 108 (range, 10-169) months. The living patients underwent complete follow-up of, at least, nine years. Fourteen patients developed local recurrence. The time to detection was longer than two years in eight cases and longer than five years in four. Twenty-one patients developed metastases, 19 within the first five years from surgery. At the univariate analysis, clinical stage at presentation, lymph node involvement at clinical restaging after neoadjuvant therapy, and pT and pN stage were found positively correlated to the incidence of metastases. At the multivariate analysis, the only factors which confirmed a positive correlation were pT stage and pN stage. The actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4 percent, respectively. The same figures for cancer-related survival were 77.9, 70, and 65.8 percent. At the univariate analysis, factors directly correlated with worse survival were: TNM stage at clinical restaging after neoadjuvant therapy (in particular lymph node involvement) pTNM, pT, and pN. At the multivariate analysis the only factors that confirmed a correlation with worse survival were pTNM, pT, and pN. CONCLUSIONS: Long- term follow-up allows to individuate 28 percent of all local relapses after the first five years from surgery. Postoperative stage is highly predictive of prognosis.

Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma.

In the present study, the prognostic impact of factors involved in the apoptosis pathway were tested on 67 consecutive patients treated with surgical resection. Included in the study were all patients resected for pancreatic adenocarcinoma from 1988 to 2003. Expression analysis for p53, Bax, and Bcl-2 were performed by immunohistochemical staining. Apoptotic cells were identified by the TUNEL method. These data were correlated with survival. Sixty-seven tumor specimens were included in the study. A strong positive correlation was recorded between p53 overexpression and Bax expression levels (P < 0.001). By univariate analysis, overall survival seemed to be improved with Bcl-2 and Bax expression (respectively, P = 0.0379 and 0.0311). The median survival time in patients with low apoptotic index was better versus those with a high index (P = 0.0127). Lymph node involvement was the only clinico-pathologic parameter that significantly correlated with overall survival (P = 0.0202). By a multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was the apoptotic index (P = 0.040). Tumor's overexpression of both Bax and Bcl-2 resulted the strongest independent prognostic factor (P = 0.013). This is the first study to report a statistically significant association of apoptosis to overall survival for pancreatic cancer patients treated with surgical resection. The contemporary overexpression of Bax and Bcl-2 represents the strongest prognostic factor.

Synchronous bilateral breast carcinoma in a 50-year-old man with 45,X/46,XY mosaic karyotype: report of a case.

We report a case of synchronous bilateral breast cancer in a patient with ambiguous external genitalia attributed to a 45,X/46,XY mosaicism. To our knowledge, this represents the first such case ever to be reported. Mammography, ultrasonography, computed tomography, and magnetic resonance imaging all showed bilateral suspicious breast masses with microcalcifications. There were no radiological findings of muscle invasion or axillary lymphadenopathy. The patient was successfully treated by bilateral radical modified mastectomy followed by external irradiation and adjuvant endocrine therapy. Histological examination revealed a bilateral ductal carcinoma in situ, with a cribriform and papillary pattern and microfoci of infiltrating ductal carcinoma. The hormonal profile revealed high levels of follicle-stimulating hormone and luteinizing hormone, and low levels of testosterone. Testicular sonography revealed small hypoechoic testicles with bilateral microlithiasis. This case shows that 45,X/46,XY men may have an increased risk of breast cancer and must be followed up carefully.

Surgical treatment and MRI in phyllodes tumors of the breast: our experience and review of the literature.

AIMS: To reassess the relationship between magnetic resonance imaging (MRI) findings and surgical resection margins in an attempt to address the issue of appropriate surgical management of phyllodes tumors (PT). METHODS: Three female patients with a large palpable mass suspicious for phyllodes tumors were studied by mammography (MX), ultrasound (US) and dynamic MRI and then underwent surgery. RESULTS: MRI demonstrated a rapidly and markedly enhancing multi-lobulated lesion. T1-weighted and T2-weighted sequences showed inhomogeneous signal intensity for the presence of cystic areas with internal septation and hemorrhage. Some areas of linear enhancement were present around the mass only in one case. Surgical management was mastectomy in one patient and wide excision in the other two patients. The margins in one of the latter patients were not clear, so mastectomy with immediate prosthetic reconstruction was subsequently performed. Pathological results showed 1 case of benign phylloides tumor, 1 case of borderline phylloides tumor and 1 case of malignant phylloides tumor. CONCLUSIONS: MRI enabled complete visualization of the tumor even in the region close to the chest wall, as well as clear delineation from healthy glandular tissue and may help to define the appropriate surgical management of phylloides tumor.

Impact of emergency surgery in the outcome of rectal and left colon carcinoma.

The negative results in terms of morbidity, mortality and survival among emergency treated patients affected by colorectal cancer are well known. The specific contribution of emergency surgery to adverse outcome is not clear because of the presence in all series of other possible determinants of a poor prognosis. We used a case-control study design to compare a group of 50 patients operated on for cancer of the rectum and left colon presented as emergencies in our department during the last 14 years, and an equal number of patients who underwent elective procedures during the same period. All records of these patients were reviewed and matched for age, stage, tumor location, and medical comorbidities (coronaropathy, diabetes mellitus, cerebral vascular deficiency, chronic obstructive pulmonary disease). Outcome measures included length of hospital stay, morbidity, mortality, and actuarial 5-year survival. Univariate and multivariate analysis of factors potentially influencing survival was performed on the entire population of 100 patients. Age, tumor location, stage of disease, and medical comorbidities were well matched by intent of the study design. Overall surgical morbidity (44% versus 12% P = 0.0004), length of hospital stay (16, 64 versus 10, 97 days P = 0.0026) and postoperative mortality (4% versus 0% P = 0.4949) resulted higher in the emergency group. Actuarial overall 5-year survival was not different between the two groups. The only variables independently predictive of survival in multivariate analysis were age and rectal location of the tumor. Postoperative surgical mortality and long-term survival appear not to be influenced by emergency presentation of colorectal cancer; the negative impact of the emergency procedures is confined to the immediate postoperative period and is probably connected to the acute medical pathology often presented by patients in emergency situations. Dealing with this kind of patient's accurate preoperative assessment and solution of acute medical pathologies before surgical treatment are mandatory.

The multidisciplinary rectal cancer treatment: main convergences, controversial aspects and investigational areas which support the need for an European Consensus.

BACKGROUND AND PURPOSE: During the past decades staging and treatment of rectal cancer are used different in Europe and in North America. To promote a process to integrate the daily practice with the best evidence of the literature an International Conference was organized in Italy. Agreement between Experts, Centres, and specialists who participated in the Conference are reported. METHODS: Five aspects were analyzed and a questionnaire was tailored for this purpose. The questionnaire had 159 questions. During the Conference, at the beginning of each Session, the moderators showed the answers from the Experts and the Centres, and, at the end of the session, the audience voted in all controversial issues. Agreements were scored at three levels: minimum, if it was between 51 and 74% of votes for each group; moderate, between 75 and 94%; large, more than 94%. RESULTS: The main results are: staging: endoanal ultrasound was considered as mandatory in T staging, in the evaluation of sphincter infiltration, and in the restaging of T after chemoradiotherapy (chRT). Magnetic Resonance Imaging is mandatory in the evaluation of mesorectal fascia infiltration. Endoscopy had a moderate agreement for the definition of tumour location, and the barium enema as optional. Digital rectal examination is complementary for staging and PET-CT investigational for T, N and yT staging. Preoperative radiotherapy: for T4 stage chRT was always the preferred treatment, often with moderate agreement, for any tumour location and N status. For T3, chRT received the same agreement except for high location and N0-N1. For T2 stage, N2 and positive nodes outside the mesorectum, chRT received minimum agreement for low and middle tumours; for high tumours only positive nodes outside the mesorectum was agreed upon. Preoperative radiotherapy, negative specimen and sphincter preservation: chRT was agreed by many for all T stages and N presentations of lower third tumours, except for T1-2 N0-N1. Postoperative treatments: the selection for these treatments often received moderate agreement according to the infiltration of surrounding organs, positive nodal status and circumferential radial margins. Therapy of metastatic disease: an agreement was found for FOLFOX as first-line therapy and for FOLFIRI as second-line, although comparative studies show similar activity of FOLFOX and FOLFIRI regimens. CONCLUSIONS: This process represents an expertise opinion process that may contribute to increased scientific debate and to promote the development of 'guidelines', 'clinical recommendations' and ultimately a Consensus on the evolving approach to rectal cancer treatment.

Metastatic tumors of the umbilicus: report of two cases and review of the literature.

An umbilical nodule may be an early or late sign of metastatic spread from an internal malignancy. Usually it appears when the internal malignancy is widely disseminated and has been previously diagnosed. More rarely, such a nodule is the first sign of disease and eventually results in the diagnosis of the primary tumor. We present two cases which document examples of both events, in order to focus on the most relevant aspects of this condition.

Cyclooxygenase-2 overexpression is associated with a poor outcome in resected ampullary cancer patients.

PURPOSE: To identify potential prognostic molecular factors in ampullary adenocarcinoma that could be of significant importance. To this end, we examined the possible prognostic significance of cyclooxygenase-2 (Cox-2) and Survivin expression and the apoptotic index in a cohort of uniformly treated patients with ampullary cancer treated with radical surgical excision. EXPERIMENTAL DESIGN: The entry criteria were that the patients have a pathologic diagnosis of ampullary cancer which had been resected. Expression analysis for Cox-2 and Survivin was done by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. RESULTS: Thirty-nine tumor specimens from resected ampullary adenocarcinoma patients were included. By univariate analysis, overall survival was affected by Cox-2 expression and TUNEL staining (respectively, P = 0.0003 and 0.03). Survivin expression did not influence the overall survival in our patient population (P = 0.123). Patients' clinicopathologic features (gender, age, and T and N factors) did not influence outcome. In multivariate Cox regression analysis, Cox-2 expression (relative risk, 4.330; P = 0.005) was the only variable that significantly affected overall survival. CONCLUSIONS: The results of the present article provide, for the first time, evidence that Cox-2 expression, but not Survivin expression, may represent a significant prognostic factor after surgical resection in patients affected by cancer of the ampulla of Vater. Further studies are required to determine whether Cox-2 inhibitors may be useful for the therapy or prevention of ampullary carcinoma.

Prognostic indicators in locally advanced gastric cancer (LAGC) treated with preoperative chemotherapy and D2-gastrectomy.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy is increasingly considered an effective treatment option for patients with gastric carcinoma. Aim of the study is to evaluate the prognostic significance of the pathological response and of known prognostic factors in a group of accurately staged locally advanced gastric cancer (LAGC) patients. METHODS: Thirty-three patients with LAGC, staged by laparoscopy, underwent D2-gastrectomy after preoperative chemotherapy. Survival was calculated by Kaplan-Meier method and differences were assessed by the Log-rank and Breslow test. Multivariate analysis was performed using the Cox proportional hazard model in backward stepwise regression. RESULTS: Curative resection (R0) was achieved in 81.8% of patients. A complete or subtotal pathological response was documented in 3 and 6%, respectively. Nineteen out of thirty-three (57.6%) patients were alive and 16 of them were free of relapse at last follow-up. Survival rates were 81, 67, and 59% at 12, 24, and 36 months, respectively. At univariate and multivariate analysis, only R0 resection was found to be an independent prognostic factor. CONCLUSIONS: In the current study, R0 resection is the most important prognostic factor for resectable LAGC; according to our results we feel encouraged to consider neoadjuvant chemotherapy a promising modality for increasing the R0-percentage of gastric carcinoma patients who could benefit from a curative surgery.

Chemoradiation with raltitrexed and oxaliplatin in preoperative treatment of stage II-III resectable rectal cancer: Phase I and II studies.

PURPOSE: Two separate studies were conducted, the first to evaluate the maximal tolerated dose and the second the efficacy of raltitrexed plus oxaliplatin in conjunction with preoperative chemoradiation in patients with resectable T3 rectal carcinoma. METHODS AND MATERIALS: A total of 48 patients received radiotherapy (50 Gy) administered to the posterior pelvis 5 d/wk for 5 weeks. Combination raltitrexed (3 mg/m(2)) and oxaliplatin (60 to 130 mg/m(2)) was administered on Days 1, 19, and 38. RESULTS: The recommended dose of oxaliplatin is 130 mg/m(2) (maximal tolerated dose not reached). No patients developed Grade 4 acute toxicity. Grade 3 acute toxicity occurred in 9 patients (18.7%). It was hematologic in 1 patient and GI in 1 patient; 7 patients had an asymptomatic increase of transaminase. Surgery was performed in 47 (98%) of 48 patients. Of the 47 patients, 42 underwent sphincter-saving surgery; in 19, the tumor at diagnosis was located <30 mm from the anorectal ring. Chemoradiation in combination with raltitrexed and oxaliplatin produced high rates of tumor response. The overall tumor downstaging rate was 73% for T and N stages. A complete pathologic tumor response (pT0) or microscopic tumor foci (pTmic) was observed in 28 patients. The tumor regression grade (TRG), using the Mandard scoring system, was TRG1 in 16 patients (43.2%), TRG2 in 12 (32.4%), TRG3 in 12 (32.4%), TRG4 in 6 (16.2%), and TRG5 in 1 patient (2.7%). CONCLUSION: Raltitrexed plus oxaliplatin combined with pelvic radiotherapy was effective and well tolerated in patients with resectable T3 rectal carcinoma.

Combined-modality therapy in locally advanced primary rectal cancer.

PURPOSE: Patients with unresectable, locally advanced rectal cancer are reported to have a dismal prognosis. The aim of this study was to analyze the effect of combined-modality therapy on clinical outcome. METHODS: From March 1990 to December 1997, 43 patients (28 males; median age, 62 years; median follow-up, 74 months) with locally advanced (T4 and/or N3) nonmetastatic rectal cancer received external-beam radiation (23.6 plus 23.6 Gy (split course), 8 patients; 45 Gy, 35 patients) plus 5-fluorouracil (96-hour continuous infusion, Days 1-4, at 1,000 mg/m(2)/day) and mitomycin C (10 mg/m, intravenous bolus, Day 1). Concomitant chemotherapy was repeated at the beginning of the second course (split-course group) or in the last week of radiotherapy (continuous-course group). After 6 to 8 weeks, patients were evaluated for surgical resection and intraoperative radiation therapy (10 to 15 Gy). Thereafter, adjuvant chemotherapy (5-fluorouracil plus leucovorin, 6-9 courses) was prescribed. RESULTS: During chemoradiation, 5 patients (11.6 percent) developed Grade 3 to 4 hematologic toxicity. After chemoradiation, 29 patients (67.4 percent) had an objective clinical response (complete response, 2.3 percent; partial response, 65.1 percent). Thirty-eight patients underwent radical surgery (anterior resection, 24 patients; abdominoperineal resection, 14 patients; intraoperative radiation therapy boost on the tumor bed, 19 patients), and 2 patients had partial tumor resection. No perioperative deaths occurred in the patient group. Five-year survival and local control rates were 59.9 and 69.1 percent, respectively. Distant metastasis occurred in 44.2 percent of patients. Statistically significant relationships between intraoperative radiation therapy and local control (P = 0.0104), radical surgery and survival (P = 0.0120), and adjuvant chemotherapy and disease-free survival (P = 0.0112) were observed. CONCLUSIONS: Our data suggest that combined-modality therapy was relatively well tolerated and resulted in good local control and survival. With regard to the impact of surgical resection on survival, additional studies aimed at improving the local response rate are necessary, whereas the positive impact of intraoperative radiotherapy on local control appears to justify the inclusion of this therapeutic modality in prospective multi-institutional trials.

A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease.

BACKGROUND & AIMS: This study was undertaken to prospectively compare the clinical outcomes of small bowel radiographs with the wireless capsule endoscopy. METHODS: Twenty-two patients were selected consecutively because of suspected small bowel disease. Two patients were excluded owing to ileal stenosis. Thus, the results of barium follow-through and the Given M2A wireless video capsule (Given Imaging Ltd., Yoqneam, Israel) endoscopy were compared in 20 patients (13 men; mean age, 52.5 yr; range, 29-78 yr). RESULTS: Barium follow-through was normal in 17 patients and showed ileal nodularity in 3 patients. Capsule endoscopy was normal in 3 patients and showed positive findings in the remaining 17 patients. The barium study was considered diagnostic in 4 (20%) patients. The capsule endoscopy was considered diagnostic in 9 (45%) patients, suspicious in 8 (40%) patients, and failed in 3 (15%) patients. For obscure gastrointestinal (GI) bleeding, the diagnostic potential of barium follow-through was much worse as compared with the capsule endoscopy (5% vs. 31%, P < 0.05). Capsule endoscopy was well tolerated and better accepted by patients when compared with the most recently performed endoscopic procedure. CONCLUSIONS: The video capsule endoscope was found to be superior to small bowel radiograph for evaluation of small bowel diseases. However, this novel wireless endoscope system needs further assessment because of limitations such as difficulties in interpretation of potentially nonspecific findings.