Acquired resistance to an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in an uncommon G719S EGFR mutation.

Background Acquired resistance (AR) to an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is a common event, and several underlying mechanisms, including T790 M, MET amplification and PTEN downregulation, have been reported for the common EGFR mutations. EGFR G719X is an uncommon mutation that has been reported to show sensitivity to EGFR-TKIs. However, no established cell lines harboring the EGFR G719X have been reported in the literature. Materials and Methods G719S-GR cells were established from malignant pleural effusion of a patient whose tumor developed AR from gefitinib treatment. G719S-GR cells were then genotyped and tested for drug sensitivities. Multiplex ligation-dependent probe amplification (MLPA) was used to compare the clinical tumor samples with G719S-GR. Results G719S-GR cells were resistant to EGFR-TKIs with an LC50 of around 10 µM. A genomic analysis showed that G719S-GR cells harbor the EGFR G719S mutation as well as the amplification of EGFR locus. The homozygous deletion of CDKN2A and the loss of PTEN and TSC1 were also detected. On comparing the copy number of tumor suppressor genes using MLPA, G719S-GR cells were found to lack one copy of PTEN, which was not observed in a tumor obtained before gefitinib treatment. Loss of PTEN may result in AKT activation. The mTORC1/2 inhibitor Torin-1 was able to inhibit the downstream signaling when combined with osimertinib. Discussion The newly established G719S-GR cell line may be useful for investigating the mechanism underlying the development of AR in the G719X mutation; the loss of PTEN may be one such mechanism.

Sarcomatoid carcinoma of the remnant stomach: report of a case.

We herein report a case of sarcomatoid carcinoma that developed in a remnant stomach. A 76-year-old male with a history of distal gastrectomy for a duodenal ulcer 28 years earlier underwent investigation for a tumor in the remnant stomach. An endoscopic survey showed a round elevated tumor measuring 6 cm in diameter, and a biopsy specimen suggested carcinosarcoma. A total gastrectomy of the remnant stomach was performed, and the excised tumor was identified to be a malignant neoplasm consisting of both carcinomatous and sarcomatous components. A diagnosis of sarcomatoid carcinoma was made since the epithelial markers were positive even in the mesenchymal elements of the tumor. To our knowledge, only 4 cases of sarcomatoid carcinoma of the stomach have been reported in the English literature so far.

Liver metastases 2 years after resection of a very-low-risk duodenal gastrointestinal stromal tumor: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, but are the most common mesenchymal tumors of the gastrointestinal tract. The risk classification of GISTs is based on the tumor size, mitotic index, tumor site, and presence of tumor rupture. Recurrence in the very-low-risk group is extremely rare. We herein report a case of liver metastases 2 years after resection of a very-low-risk duodenal GIST. CASE PRESENTATION: A 57-year-old woman presented to the hospital for evaluation of melena. Esophagogastroduodenoscopy showed bleeding from the exposed blood vessels at the top of a submucosal tumor approximately 20 mm in size located in the second (descending) part of the duodenum, and the bleeding was controlled with electrocoagulation. A GIST was suspected, and the patient underwent wedge resection of the duodenum. The resected specimen contained a 16- × 12-mm (< 20-mm) white submucosal tumor composed of spindle cells with a mitotic count of 4 per 50 high-power fields, and a histologically negative margin was achieved. Immunochemical analysis revealed positive tumor staining for c-kit protein and alpha-smooth muscle actin and negative staining for CD34, desmin, and S-100 protein. Therefore, the tumor was diagnosed as a very-low-risk duodenal GIST based on the Fletcher classification and modified Fletcher classification (Joensuu classification). The postoperative course was uneventful, and the patient was discharged on postoperative day 11. At the follow-up visit 2 years postoperatively, contrast-enhanced computed tomography revealed liver tumors in S8 and S6 measuring 26 × 24 and 10 × 10 mm, respectively. Both lesions showed peripheral dominant hyperenhancement with hypoenhancement inside, indicating tissue degeneration within the tumors. These imaging findings closely resembled those of the duodenal GIST. Hence, the patient was diagnosed with liver metastases of GIST 2 years postoperatively. She was subsequently started on treatment with 400 mg of imatinib. At the time of this writing (2 months after diagnosis), the patient was clinically well and asymptomatic and was continuing imatinib therapy. CONCLUSIONS: Recurrence of very-low-risk GISTs is extremely rare. Even a small GIST with low mitotic activity can never be considered completely benign, and long-term follow-up is necessary.

Clinical significance of part-solid lung cancer in the eighth edition TNM staging system.

OBJECTIVES: The ground-glass component of part-solid tumour (PST) was eliminated as a clinical T (cT) descriptor in the eighth edition of the tumour, node and metastasis (TNM) staging system. We aimed to validate the new cT descriptor and investigate the prognostic impact of PST in the new staging system. METHODS: Non-small-cell lung cancer (NSCLC) patients (n = 1061) who underwent lung resection and were available for the assessment of thin-section computed tomography images were retrospectively reviewed. Tumours with a solid component (SC) size-to-whole tumour size (STR) ratio of 0, those with 0 < STR < 1 and those with an STR of 1 were defined as pure ground-glass tumours, PSTs and solid tumours (STs), respectively. RESULTS: Tumours with an SC diameter of >30 mm were less frequently observed among PSTs than among STs (4.83% vs 32.6%, P < 0.001). The postoperative 5-year survival of NSCLC patients with ground-glass tumour, PST and ST was 97.6%, 89.0% and 76.3%, respectively. In the survival analysis of patients with an SC diameter ≤30 mm, significant differences were observed among PST and ST (5-year survival, 90.7% vs 74.6%, P < 0.001). The multivariable analysis showed that age <70 years old, female sex, procedures with a lobectomy or more, SC size, pN0 disease and PST were independent predictors of a better survival among all PST and ST patients. CONCLUSIONS: Among patients with cT1 tumours, those with PST showed a significantly better survival than did those with ST. Small-sized PST tumours may not be suitable for the new cT descriptor.

Thymoma-associated myasthenia gravis coexisting with myotonic dystrophy: a case report.

BACKGROUND: Myotonic dystrophy (dystrophia myotonica [DM]) is an autosomal-dominant inheritance, and myasthenia gravis (MG) is an autoimmune disease characterized by weakness of skeletal muscles. Cases of both DM and MG are extremely rare and distinguishing DM and MG symptoms is challenging. CASE PRESENTATION: We herein report a 49-year-old woman presenting with subacute dyspnea and muscle weakness. She had previously been diagnosed with DM 24 years earlier. Computed tomography (CT) revealed an anterior mediastinal 32-mm solid mass that was suspected of being thymoma. The clinical features and neurological examination findings confirmed the diagnosis of thymoma-associated MG coexisting with DM. Intensive treatment for MG, including surgery, resulted in an improvement in some of her neurological symptoms. CONCLUSIONS: The symptoms of DM usually progress slowly, so the sudden exacerbation of symptoms indicates the involvement of other factors. It is important to be aware of these associations, as an early diagnosis with proper treatment will result in a better outcome.

Resection and postoperative radiation therapy for desmoid fibromatosis of the chest wall in a young woman.

BACKGROUND: Surgery is an effective treatment for desmoid fibromatosis, but it may be difficult, depending on the location or local spread of the tumor, and the decision to perform surgery must be made carefully. We herein report a case of desmoid fibromatosis of the chest wall in a young woman suspected of having invasion to the 1st, 2nd and 3rd ribs. CASE PRESENTATION: A 35-year-old woman had been aware of dry cough and right chest pain, so she was referred to our hospital. Chest computed tomography showed a localized pleural tumor mainly at the first rib. Magnetic resonance imaging revealed a 75 × 65 × 27-mm tumor with a smooth surface, with partial contact from the first rib to third rib and partial extension to the 1st intercostal space. The tumor showed growth in the two months after the first visit, so resection was performed. The tumor was completely resected, and adjuvant radiation therapy (50 Gy) was performed for the small margin. The pathological diagnosis was desmoid fibromatosis. The postoperative course has been uneventful, without recurrence at 14 months after surgery. CONCLUSIONS: In chest wall tumors located ventral of the pulmonary apex, we suggest that a combination of the Grunenwald method and Masaoka anterior approach may be a useful option. In cases where margin is not enough, adjuvant radiation therapy should be considered.

Primary neuroendocrine carcinoma coexisting with hemangioma in the liver: report of a case.

Primary hepatic neuroendocrine carcinoma is an extremely rare liver tumor. We herein report a case of primary hepatic neuroendocrine carcinoma coexisting with a hemangioma in a 66-year-old man. Ultrasonography, computed tomography, and magnetic resonance imaging showed a tumor (1.5 cm in diameter) coexisting with a hemangioma in the lateral segment of the liver. Liver biopsy showed malignant cells, and several examinations revealed no alternative primary source. We performed a lateral segmentectomy. Microscopically, the tumor cells had round to oval nuclei and eosinophilic cytoplasm, proliferated in thick trabeculae or solid nests, and formed a focal rosette pattern. Mitotic cells were frequently observed. Immunohistochemically, the tumor cells were positive for the endocrine markers chromogranin A, neuron-specific enolase, and neural cell adhesion molecule, but negative for alpha-fetoprotein and hepatocyte-specific antigen. The patient is still alive after 3 months, without recurrence.

Evaluating the Platelet Distribution Width-to-Plateletcrit Ratio as a Prognostic Marker for Patients With Breast Cancer.

AIM: This study aimed to evaluate plateletcrit (PCT) and platelet distribution width-to-PCT ratio (PDW/PCT) as potential prognostic biomarkers in patients with breast cancer. PATIENTS AND METHODS: Information of 337 patients was retrospectively reviewed. The Cox regression proportional hazards model was used to evaluate the prognostic value of PCT and PDW/PCT compared to the platelet distribution width-to-platelet count ratio (PDW/P) and red cell distribution width-to-platelet count ratio (RDW/P). RESULTS: Large tumor size (p<0.01), lymph node involvement, and increased PDW/P, RDW/P, and PDW/PCT (p<0.05) were significantly associated with inferior disease-free survival (DFS) according to the univariate analysis. The multivariate analysis showed that large tumor size (p<0.01) and increased PDW/PCT (p<0.05) were significant prognostic factors for poor DFS. CONCLUSION: To our knowledge, this is the first report to show that PDW/PCT is a significant prognostic factor for patients with breast cancer. Therefore, it might be an attractive biomarker providing additional prognostic information for these patients.

Elevated red cell distribution width to platelet count ratio predicts poor prognosis in patients with breast cancer.

Red cell distribution width (RDW) to platelet ratio (RPR) is a prognosticator in acute pancreatitis and myocardial infarction; however, the prognostic values of RDW and RPR in breast cancer have not been studied. This retrospective analysis of 299 breast cancer patients investigated the association between RDW and RPR and clinicopathological characteristics and prognosis, compared to platelet distribution width to platelet count ratio (PDW/P) which is a known independent prognostic factor in patients with breast cancer. We found a significant correlation between RPR, and age and HER2 status. An elevated RPR significantly correlated with age and HER2 status. After a median follow-up duration of 48 months, tumour size, nuclear grade, PDW/P, and RPR were recgnized to be significantly associated with lower disease-free survival rates (tumour size: p < 0.01; nuclear grade, PDW/P, and RPR: p < 0.05) in univariate analysis. Tumour size and RPR were significant prognostic factors for lower disease-free survival rates, with hazard ratios of 4.31 (95% confidence interval: 1.76-10.53) (p < 0.01)] and 2.79 [95% confidence interval: 1.01-87.69) (p < 0.05)], respectively, in a multivariate analysis using the Cox proportional hazards model. This is the first study showing that an elevated RPR could independently predict poor prognosis in patients with breast carcinoma. Thus, RPR could be a novel biomarker for prognostic estimation.

Erlotinib and bevacizumab combination therapy for afatinib-refractory leptomeningeal carcinomatosis from EGFR-mutated lung cancer.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors remains the main hurdle in treating EGFR-mutated lung cancer. Besides, when leptomeningeal carcinomatosis occurs during treatment, it often leads to treatment failure. We herein report a case of lung adenocarcinoma involving a patient with an EGFR exon 19 deletion mutation who developed leptomeningeal carcinomatosis after afatinib treatment for post-operative recurrence. He received right lower lobectomy, followed by four cycles of cisplatin and pemetrexed treatment. Follow-up CT/MRI revealed multiple pulmonary metastases and brain metastases at 7 months after surgery, and afatinib (40 mg/day) was administered after stereotactic radiotherapy for brain metastasis. At 28 months after surgery, follow-up MRI revealed asymptomatic leptomeningeal carcinomatosis, which was cytologically proven from the cerebrospinal fluid. Because EGFR T790M was not detected in plasma cell-free DNA or cerebrospinal fluid, erlotinib and bevacizumab combination treatment was administered. He remained asymptomatic and was radiographically clear of LM at 2 months after treatment. In comparison to other EGFR-TKIs, erlotinib shows penetrance into the cerebrospinal fluid. Furthermore, the addition of bevacizumab might enhance the treatment effect, because it is known to relieve brain edema from metastatic brain tumors by normalizing immature vascularity and improving drug penetrance into the cerebrospinal fluid by reducing interstitial fluid pressure.

Sarcopenia discriminates poor prognosis in elderly patients following emergency surgery for perforation panperitonitis.

AIM: Sarcopenia has been reported as a prognostic predictor in various conditions; however, it has not been examined in patients with perforation panperitonitis. METHODS: A total of 103 consecutive patients with perforation panperitonitis who underwent emergency surgery from 2008 to 2016 were retrospectively evaluated. Skeletal muscle index (SMI) was measured as the cross-sectional area (cm2) of skeletal muscle in the L3 region on computed tomography images normalized for height (cm2/m2). Sarcopenia was defined as an SMI of ≤43.75 and ≤41.10 cm2/m2 in men and women, respectively. The impact of sarcopenia on postoperative outcomes was investigated. RESULTS: Sarcopenia was present in 50 (48.5%) patients. Severe complications (Clavien-Dindo grade ≥IIIb) and in-hospital mortality were more frequently observed in patients with than without sarcopenia (28.0% vs 9.4%, P = .015) (20.0% vs 5.7%, P = .029) respectively. Multivariate analysis showed that age, sarcopenia, and renal dysfunction were independent risk factors for severe complications and in-hospital mortality. The optimal cut-off levels of age and SMI for predicting these were ≥79 years and SMI <38 cm2/m2, respectively. Among the patients aged ≥79 years, those with SMI <38 cm2/m2 had a severe complication rate of 71% and an in-hospital mortality rate of 57%, whereas the rate of those with SMI ≥38 cm2/m2 was 22% (P = .011) and 11% (P = .008), respectively. CONCLUSION: Sarcopenia is a predictive factor of severe complications and in-hospital mortality following emergency surgery for perforation panperitonitis, especially in elderly patients. Estimation of sarcopenia may identify patients eligible or not eligible for emergency surgery among elderly patients.

Time-dependent relevance of prognostic factors in patients with gastric cancer.

BACKGROUND/AIMS: Prognostic factors are useful for establishing a prognosis of patients from the time of operation. However, the value of individual prognostic factors may change dependent on the length of the follow-up period, and it is not clear how long these factors keep their prognostic relevance. METHODOLOGY: Data was used from 233 Japanese patients treated by potentially curative resection for primary gastric cancer, between 1993 and 1998. Survival analysis was done starting at 1-yearly intervals after operation and follow-up in the first analysis started at the time of the operation. RESULTS: Prognostic relevance of tumor size was not evident for total follow-up time but was significantly emphasized 1 year after operation. Serosal invasion lost its prognostic value within one year of operation. The status of lymph node metastases retained its ability to predict survival after 2 years' follow-up whereas after 3 years' follow-up nodal status seemed to be without significance. CONCLUSIONS: A distinct time-dependency with varied patterns was found in the influence of some prognostic factors on survival. Detecting the changing importance of prognostic factors could provide new biological insights that might otherwise be missed, and may help determine the most appropriate clinical use of various factors.

Intratumoral heterogeneity of copy number variation in lung cancer harboring L858R via immunohistochemical heterogeneous staining.

BACKGROUND: Although intratumoral heterogeneity is commonly observed in several cancers, few studies have shown its presence in EGFR-mutated lung cancer. We performed immunohistochemistry to analyze the intratumoral heterogeneity in EGFR-mutated (L858R) lung cancer and performed targeted sequencing in specific cases. We discuss the effects of intratumoral heterogeneity and acquired resistance to EGFR-TKI. METHODS: Twenty resected primary lung cancers known to harbor EGFR L858R were analyzed. IHC was performed using an L858R mutant-specific rabbit monoclonal antibody and the samples were scored by staining intensity (0-3) and proportion. For cases with heterogeneous L858R protein expression, the nucleic acids were extracted from each differently stained lesion, and targeted sequencing was performed. Single nucleotide variations (SNVs) and copy number variations (CNVs) were then analyzed. The cell proliferation and apoptosis were also evaluated by the ki-67 labeling index and TUNEL staining. RESULTS: Among 20 cases, 3 showed heterogeneous staining. Genetic analyses for cases with heterogeneous staining revealed an increase in the copy number of EGFR in the IHC-positive part compared to the negative part, and an increase in the copy number of CCNE1 was observed in the IHC-positive part compared to the negative part in one case (case 1). In another case (case 2), an increase in the copy number of EGFR was observed in the IHC-positive part compared to the negative part, and an increase in the copy number of MDM2 was observed in the IHC-positive part compared to the negative part. In three cases, no SNV changes were observed. An increase in the ki-67 labeling index in the L858R-positive part in case 1 and increased apoptosis in the L858R-positive part in case 2 were observed, suggesting the functional significance of CNV changes. CONCLUSION: These cases exhibiting L858R IHC intratumoral heterogeneity suggest a heterogeneous effect on the cell activity due to CNV heterogeneity.

The Positive Relationship Between γH2AX and PD-L1 Expression in Lung Squamous Cell Carcinoma.

BACKGROUND/AIM: Lung squamous cell carcinoma often arises from precancerous lesions where alterations in tumor suppressor genes and subsequent chromosomal instability are often observed due to carcinogen exposure. These tumors are often immunogenic; as such, immune checkpoint inhibitors are a promising therapeutic option. We hypothesized that the DNA damage response in tumor cells induces an immune response, thereby up-regulating programmed death-ligand 1 (PD-L1) expression on tumor cells, which in turn sensitizes them to anti-PD-1 therapy. PATIENTS AND METHODS: An immunohistochemical analysis was performed in 41 consecutive lung squamous cell carcinoma patients who underwent surgery at our institution between April 2013 and March 2014. RESULTS: The analysis revealed a high PD-L1 expression in 15 patients (37%) (p=0.028). The PD-L1 expression was positively associated with the nuclear γH2AX expression (p=0.02), that was confirmed by immunofluorescent staining. CONCLUSION: Our findings demonstrate that nuclear γH2AX expression is positively associated with the PD-L1 expression in lung squamous cell carcinoma.

Comparison of the prognostic values of preoperative inflammation-based parameters in patients with breast cancer.

Peripheral blood-derived inflammation-based markers, including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are indicators of prognosis in various malignant tumors. The present study aimed to identify the inflammation-based parameters that are most suitable for predicting outcomes in patients with breast cancer. Two hundred ninety-six patients who underwent surgery for localized breast cancer were reviewed retrospectively. The association between clinicopathological factors and inflammation-based parameters were investigated. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic indicators associated with disease-free survival (DFS). The NLR level correlated significantly with tumor size (P<0.05). The PLR level correlated with the expression of estrogen receptor and lymph node involvement (P<0.05). Univariate analysis revealed that lower CRP and PLR values as well as tumor size, lymph node involvement, and nuclear grade were significantly associated with superior DFS (CRP: P<0.01; PLR, tumor size, lymph node involvement, and nuclear grade: P<0.05). On multivariate analysis, CRP (hazard ratio [HR]: 2.85, 95% confidence interval [CI]: 1.03-7.88, P<0.05), PLR (HR: 2.61, 95% CI: 1.07-6.36, P<0.05) and nuclear grade (HR: 3.066, 95% CI: 1.26-7.49, P<0.05) were significant prognostic indicators of DFS in patients with breast cancer. Neither LMR nor NLR significantly predicted DFS. Both preoperative CRP and PLR values were independently associated with poor prognosis in patients with breast carcinoma; these were superior to other inflammation-based scores in terms of prognostic ability.

The prognostic impact of the platelet distribution width-to-platelet count ratio in patients with breast cancer.

Activated platelets promote tumor cell growth, angiogenesis, and invasion. Platelet activity can be inferred by platelet volume indices (PVIs), which include platelet distribution width (PDW), mean platelet volume (MPV), platelet distribution width-to-platelet count ratio (PDW/P), and mean platelet volume-to-platelet count ratio. Platelets and platelet-related markers, such as the platelet-to-lymphocyte ratio, have been found to be significant prognostic factors in patients with breast cancer. However, the role of PVIs for predicting survival in breast cancer remains unknown; hence, we performed this retrospective analysis of 275 patients with breast cancer. PVIs were compared with clinicopathological variables, and were assessed to identify independent indicators associated with disease-free survival (DFS) using the Cox proportional hazards model. An elevated PDW/P significantly correlated with age and HER2 status. Univariate analysis revealed that elevated PDW, MPV, and PDW/P as well as tumor size, nuclear grade, and lymph node involvement were significantly associated with inferior DFS rates (tumor size: p<0.01; nuclear grade, lymph node involvement, PDW, MPV, and PDW/P: p<0.05). On multivariate analysis, a large tumor size and elevated PDW/P were significant prognostic factors for DFS, with hazard ratios of 3.24 (95% confidence interval [CI]: 1.24-8.47) and 2.99 (95% CI: 1.18-7.57), respectively (p<0.05). Our study is the first to reveal that an elevated PDW/P significantly reduces DFS in patients with breast carcinoma. Measuring the PDW/P is simple, relatively inexpensive, and almost universally available using routine blood counts; this makes it an attractive biomarker for improved risk assessment.

Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer.

BACKGROUND: Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated. METHODS: The immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously. RESULTS: The Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS. CONCLUSION: The Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer.

Prediction of survival from first recurrence of breast carcinoma in Japanese women.

The clinical courses of patients with recurrent breast carcinoma vary greatly. We retrospectively examined data on 1863 Japanese patients treated for a breast carcinoma from 1981 to 2000. Among them, 345 (18.5%) who had clearly died of recurrence were reviewed. Patients died most frequently (63.2%) up to 30 months after the first recurrence. Based on multivariate analysis, the four factors that were most predictive of survival after the first recurrence were disease-free interval, site of recurrence, progesterone receptor (PgR) status, and vascular involvement. These findings showed that the intrinsic tumor biology of the initial primary tumor plays a critical role in determining survival after the first recurrence in patients with a breast carcinoma. The combined analysis of disease-free interval, site of recurrence, PgR status, and vascular involvement may assist in estimating the median survival after first recurrence, and may assist with the designing of new therapeutic strategies for patients with recurrence for whom there is an unfavorable prognosis.

Prediction of early and late recurrence in patients with breast carcinoma.

BACKGROUND: The clinical course of patients with recurrent breast carcinoma varies greatly. Better characterization of an individual's clinical course for recurrent patients may aid in their clinical management. However, less attention has been paid to evaluating factors associated with the timing of recurrence in those patients. We investigated the clinicopathological indicators that determined the timing of recurrence by univariate and multivariate analysis. METHODS: We retrospectively examined data on 1428 curatively treated Japanese patients who had been surgically treated for breast cancer between 1983 and 2002. From these, 244(17.1%)who had clearly died of recurrence were entered into this study. RESULTS: By univariate analysis, tumor size, estrogen receptor(ER), and progesterone receptor(PgR)were significantly correlated with time to recurrence. Multivariate analysis indicated that the time between operation and recurrence was independently influenced by ER and PR. CONCLUSIONS: Our research shows that ER and PgR are independent factors influencing the timing of recurrence of breast carcinoma after curative resection. The combined analysis of these independent factors facilitates prediction of the time to recurrence for each patient.

Surgical results of total pelvic exenteration for locally advanced colorectal adenocarcinoma.

BACKGROUND/AIMS: Although total pelvic exenteration (TPE) may lead to local tumor control and improved quality of life in patients with locally advanced colorectal cancer, an adequate understanding of prognostic factors, indications and potential complications associated with these procedures is needed. METHODOLOGY: Records for 15 patients, who underwent TPE for colorectal adenocarcinoma at Oita Prefectural Hospital between January 1983 and November 2001, were reviewed, retrospectively. RESULTS: Ten (66.7%) had positive lymphatic involvement, seven (46.7%) had positive vascular involvement, and three (20%) had positive lymph node metastases. Bladder involvement histologically was evident in eight patients (53.3%). With regard to diagnostic assessment of bladder involvement using CT, the sensitivity and specificity were 83.3% and 60%, respectively. Six of 15 patients (40%) developed complications. Overall local recurrence was observed in 6 (40%) of the 15. The cumulative overall 5-year survival rate of the 15 patients in this study was 54.7%. In the univariate analysis, vascular involvement significantly influenced survival. CONCLUSIONS: TPE appears to be relatively safe and effective for treatment of locally advanced colorectal adenocarcinoma. Vascular involvement was recognized as the only reliable prognostic clinicopathological characteristic.