Animal models and treatment of prostate cancer

Model systems for prostate cancer in rats have been developed and used for investigations on tumor biology and therapy. The "Pollard tumors" provide a combination of in vitro and in vivo attributes by which investigations can be directed at local tumor development and spontaneous metastasis. The evolution and early applications of this model system are reviewed, and the therapeutic benefits of delayed release of cyclophosphamide are presented.     

Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score

Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.     

Surgical Treatment and Proposed Modified Classification for Harrington Class III Periacetabular Metastases

ObjectivesThis study aims to: (i) evaluate the outcome of patients with Harrington class III lesions who were treated according to Harrington classification; (ii) propose a modified surgical classification for Harrington class III lesions; and (iii) assess the efficiency of the proposed modified classification.MethodsThis study composes two phases. During phase 1 (2006 to 2011), the clinical data of 16 patients with Harrington class III lesions who were treated by intralesional excision followed by reconstruction of antegrade/retrograde Steinmann pins/screws with cemented total hip arthroplasty (Harrington/modified Harrington procedure) were retrospectively reviewed and further analyzed synthetically to design a modified surgical classification system. In phase 2 (2013 to 2019), 62 patients with Harrington class III lesions were classified and surgically treated according to our modified classification. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) 93 scoring system. The outcome of local control was described using 2‐year recurrence‐free survival (RFS). Owing to the limited sample size, we considered P < 0.1 as significant.ResultsIn phase 1, the mean surgical time was 273.1 (180 to 390) min and the mean intraoperative hemorrhage was 2425.0 (400.0 to 8000.0) mL, respectively. The mean follow‐up time was 18.5 (2 to 54) months. Recurrence was found in 4 patients and the 2‐year RFS rate was 62.4% (95% confidence interval [CI] 31.6% to 93.2%). The mean postoperative MSTS93 score was 56.5% (20% to 90%). Based on the periacetabular bone destruction, we categorized the lesions into two subgroups: with the bone destruction distal to or around the inferior border of the sacroiliac joint (IIIa) and the bone destruction extended proximal to inferior border of the sacroiliac joint (IIIb). Six patients with IIIb lesions had significant prolonged surgical time (313.3 vs 249.0 min, P = 0.022), massive intraoperative hemorrhage (3533.3 vs 1760.0 mL, P = 0.093), poor functional outcome (46.7% vs 62.3%, P = 0.093), and unfavorable local control (31.3% vs 80.0%, P = 0.037) compared to the 10 patients with IIIa lesions. We then modified the surgical strategy for two subgroup of class III lesions: Harrington/modified Harrington procedure for IIIa lesions and en bloc resection followed by modular hemipelvic endoprosthesis replacement for IIIb lesions. Using the proposed modified surgical classification, 62 patients in the phase 2 study demonstrated improved surgical time (245.3 min, P = 0.086), intraoperative hemorrhage (1466.0 mL, P = 0.092), postoperative MSTS 93 scores (65.3%, P = 0.067), and 2‐year RFS rate (91.3%, P = 0.002) during a mean follow‐up time of 19.9 (1 to 60) months compared to those in the phase 1 study.ConclusionThe Harrington surgical classification is insufficient for class III lesions. We proposed modification of the classification for Harrington class III lesions by adding two subgroups and corresponding surgical strategies according to the involvement of bone destruction. Our proposed modified classification showed significant improvement in functional outcome and local control, along with acceptable surgical complexity in surgical management for Harrington class III lesions.     

Two hepatic cavernous hemangiomas mimicking colorectal liver metastasis: A rare case report

Introduction¹ Hepatic cavernous hemangioma (HCH) is a common benign lesion of the liver. The radiological features of HCH can resemble those of hepatic malignancies such as metastatic liver cancer, which make the preoperative definitive diagnosis difficult.Presentation of caseWe report the case of a 77-year-old woman who presented with a 2-month history of abdominal pain and per rectum fresh bleeding. The initial diagnosis at the referral hospital, based on computed tomography (CT) scan of the chest, abdomen, and pelvis, was sigmoid colon cancer with liver metastasis. Further evaluation at our hospital, the patient underwent colonoscopy and biopsy. Histopathological examination of the biopsy revealed an invasive moderately differentiated adenocarcinoma. The patient underwent laparoscopic sigmoidectomy and left hepatectomy. The histopathological examination of the sigmoid colon mass revealed an invasive moderately to poorly differentiated adenocarcinoma. One out of twenty lymph nodes is positive for metastatic carcinoma. The pathological stage is pT3, pN1a, pM0. The histopathological examination of the left hepatic lobe revealed two hyalinized cavernous hemangiomas with no malignancy is seen. The postoperative recovery was uneventful, and the patient was discharged home with regular follow-up in our outpatient clinic.DiscussionHCH is congenital vascular malformation and is the most common benign hepatic tumors. Fine-needle biopsy during diagnostic laparoscopy for undiagnosed multiple liver tumor can differentiate atypical HCH from colorectal metastasis but can potentially lead to rupture or seeding of cancer cells.ConclusionSurgical resection is necessary to determine if the mass is malignant in some atypical HCH mimicking liver metastasis to confirm the diagnosis with histopathologic examination.     

Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.     

Quantitative analysis of distribution and fate of human lung cancer emboli labeled with 125I-5-iodo-2′-deoxyuridine in nude mice

The chemical and radio toxicity of ¹²⁵-5-iodo-2-deoxyuridine (¹²⁵IUDR) on 870127T human lung cancer (HLC) cells grown in tissue cultures and the quantitative analysis of the distribution and fate of ¹²⁵IUDR-labeled 870127T HLC cells in nude mice were evaluated. After 870127T HLC cells were plated and ¹²⁵IUDR was added to the dishes at levels ranging from 0.1 µCi/ml to 5.0 µCi/ml of media, the growth rate of the cells for 24h was similar to that of non-labeled cells. Nude mice were given intravenous injections of ¹²⁵IUDR labeled 870127T HLC cells and killed at various intervals ranging from 5 min to 24 h after injection. Organs were collected, processed, and monitored. The lung contained most of the tumor cells at all intervals and the number of tumor cells in the lung decreased gradually post-injection. The tumor cells died rapidly, and only about 1.5% of all cell survived after 24 h post-injection. This study confirmed that very few surviving tumor cells are needed to cause metastasis.     

Survival effect of systemic therapy on patients developing metastatic breast carcinoma

A multivariate analysis was performed to assess the effect of post-relapse systemic therapy on a series of patients with metastatic breast cancer who at initial presentation had no detectable metastases (M), were 70 years of age, presented with unilateral localized disease and no other associated malignancy, and were treated between 1965 and 1984 with successive protocols for primary disease and subsequently developed distant metastasis. All 760 patients analyzed relapsed with at least one metastasis, and were studied retrospectively with no selection criteria according to any specific protocol. All had recorded clinical data on menopause, stage, clinical tumor aggressiveness (PEV), initial chemo or hormonal therapy, and time to relapse, and had ongoing follow up at our Center, with salvage chemotherapy and/or hormonal therapy having been given to some but not all patients.A brief metastasis-free survival (p < 0.000001), and factors associated with electing pre-relapse chemotherapy (p < 0.000001) were associated with shortened post-relapse survival, while post-relapse therapy (chemo p < 0.0001, and hormonal p < 0.00001, replacing chemotherapy in the model) apparently increased post-relapse survival in the group overall. This result was similar in the inoperable patient group [with inflammatory breast carcinoma an additional risk factor (p < 0.0005)], as well as the operable group. However, in the operable group, when the pathologic criteria of histologic grade and nodal status were introduced into the analysis, post-relapse therapy was not seen to be an important factor for survival in any subgroup. Histograde (p < 0.000001), nodal status (p < 0.0001), metastasis-free survival (p < 0.001), and menopausal status (p = 0.03) were the only significant factors for post-relapse survival.     

CD44v6、E-Cadherin表达与CNE-2Z-F1裸鼠移植瘤转移的关系

目的　探讨CD44v6、E -Cadherin表达与人鼻咽癌裸鼠移植瘤转移的关系。方法　分别将人鼻咽癌细胞克隆株F1在体外与鼠肺块共同孵育及胸内移植 ,然后将带瘤细胞肺块 (Ⅰ组 )和胸内瘤组织块 (Ⅱ组 )各行裸鼠皮下移植 ,并与瘤细胞悬液皮下移植瘤 (Ⅲ组 )比较 ,观察各组移植瘤转移特点。采用免疫组织化学技术检测各组移植瘤回复培养细胞CD44v6和E -Cadherin表达。结果　Ⅰ组和Ⅱ组皮下移植瘤的总转移率和淋巴结转移率均高于Ⅲ组 (其中ⅠvsⅢ ,P <0 .0 5) ;肺转移仅发生在Ⅰ组。这两组移植瘤细胞CD44v6表达水平明显增高 ,其阳性细胞数分别为 (79.7± 5.7) %、(74.1± 3.1 ) % ,第 3组为 (65.6± 4.31 ) %移植瘤转移率与CD44v6高表达密切相关 ;E -Cadherin阳性细胞分别为 (41 .7± 4.9) %、(43.8± 6.4) %和 (2 7.4± 4.9) % ,Ⅰ组、Ⅱ组与Ⅲ组之间比较 ,有显著差异 (P <0 .0 5)。结论　CD44v6的过表达和E -Cadherin功能障碍 ,可能在鼻咽癌侵袭转移中起一定作用。     

Molecular genetic studies of early breast cancer evolution

Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany.