Long-term survival after repeated resection of metachronous lung metastases from pStage IA pancreatic adenocarcinoma.

CASE REPORT: A 70-year-old woman with pancreatic ductal adenocarcinoma was initially treated by distal pancreatectomy (DP). Thirty-five months later, another tumor appeared in the pancreatic head and was treated by pancreaticoduodenectomy. Histopathological findings identified both tumors as pancreatic ductal adenocarcinoma pStage IA. Computed tomography (CT) of the chest 16 months after the second pancreatectomy revealed a ground-glass opacity in segment 3 of the right lung. Chest CT 23 months after the second pancreatectomy revealed a nodular shadow in segment 1a of the right lung. Chest CT 39 months after the second pancreatectomy revealed a nodular shadow in segment 5 of the left lung. These lesions were treated by video-assisted thoracoscopic surgery partial resection. Histopathological and immunohistochemical features (positive for cytokeratin (CK)7 and CK20, negative for transcription factor-1) for these three lesions and the secondary pancreatic ductal adenocarcinoma were similar, indicating a diagnosis of lung metastasis from the second pancreatic ductal adenocarcinoma. The patient has remained alive and free of new metastases for 8 years after initial DP, 3 years after the last lung resection. CONCLUSION: This patient has survived over the long term after undergoing three resections of lung metastases from resected pancreatic ductal adenocarcinoma.

Noninvasive management for iatrogenic splenic injury caused by chest tube insertion: a case report.

Splenic injury is one of the most critical complications of chest tube insertion and often requires invasive emergency management. However, noninvasive management such as delayed removal of the malpositioned tube may be considered for a stable patient without severe adverse event.

Risk Factors for Difficult Laparoscopic Cholecystectomy in Acute Cholecystitis.

BACKGROUND AND OBJECTIVES: Factors that contribute to difficult laparoscopic cholecystectomy (LC) in acute cholecystitis (AC) that would affect the performance of early surgery remain unclear. The purpose of this study was to identify such risk factors. METHODS: One hundred fifty-four patients who underwent LC for AC were retrospectively analyzed. The patients were categorized into early surgery and delayed surgery. Factors predicting difficult LC were analyzed for each group. The operation time, bleeding, and cases of difficult laparoscopic surgery (CDLS)/conversion rate were analyzed as an index of difficulty. Analyses of patients in the early group were especially focused on 3 consecutive histopathological phases: edematous cholecystitis (E), necrotizing cholecystitis (N), suppurative/subacute cholecystitis (S). RESULTS: In the early group, the CDLS/conversion rate was highest in necrotizing cholecystitis. Its rate was significantly higher than that of the other 2 histopathological types (N 27.9% vs E and S 7.4%; P = .037). In the delayed-surgery group, a higher white blood cell (WBC) count and older age showed significant correlations with the CDLS/conversion rate (P = .034 and P = .004). CONCLUSION: In early surgery, histopathologic necrotizing cholecystitis is a risk factor for difficult LC in AC. A higher WBC count and older age are risk factors for delayed surgery.

CD40 Expression in Human Esophageal Squamous Cell Carcinoma Is Associated with Tumor Progression and Lymph Node Metastasis.

BACKGROUND: The co-stimulatory molecule cluster of differentiation 40 (CD40) is widely expressed in various types of malignant tumors, but its role remains unclear. The purpose of this study was to investigate the relationship between CD40 expression and clinicopathological variables in patients with esophageal squamous cell carcinoma (ESCC), as well as the function of CD40 expressed on ESCC tumor cells in vitro. MATERIALS AND METHODS: Tumor specimens of patients who underwent surgical resection for ESCC were immunohistochemically analyzed for CD40 expression. RESULTS: Of the 122 specimens, 45 (37%) were positive for CD40. Significant positive correlation was found between CD40 expression and p-stage (p=0.0011), histopathological grade (p=0.0143), pT-classification (p=0.0011), and pN-classification (p=0.0007). Survival of patients with stage III and IV disease with positive CD40 expression was significantly shorter than that of those with negative expression (log-rank test, p=0.0422). In in vitro analysis, while the addition of recombinant human CD154 did not inhibit growth, it did induce a significant increase in interleukin 6 production in ESCC cell lines. CONCLUSION: These results suggest that functional expression of CD40 on tumor cells might play an important role in tumor progression and lymph node metastasis in ESCC.

Blood stasis may cause thrombosis in the left superior pulmonary vein stump after left upper lobectomy.

BACKGROUND: We previously reported that arterial infarction of vital organs after lobectomy might occur only after left upper lobectomy and be caused by thrombosis in the left superior pulmonary vein stump. We hypothesized that changes in blood flow, such as blood stasis and disturbed stagnant flow, in the left superior pulmonary vein stump cause thrombosis, and this was evaluated by intraoperative ultrasonography. METHODS: From July 2013 to April 2014, 24 patients underwent lobectomy in the Steel Memorial Muroran Hospital. During the procedure, an ultrasound probe was placed at the pulmonary vein stump and the velocity in the stump was recorded with pulse Doppler mode. The peak velocity and the presence of spontaneous echo contrast in the stump were evaluated. After the operation, the patients underwent contrast-enhanced CT within 3 months. RESULTS: The operative procedures were seven left upper lobectomies, four left lower lobectomies, seven right upper lobectomies, and six right lower lobectomies. Blood flow was significantly slower in the left superior pulmonary vein stump than in the right pulmonary vein stumps. However, that was not significantly slower than that in the left inferior pulmonary vein stump. Spontaneous echo contrast in the pulmonary vein stump was seen in three patients who underwent left upper lobectomy. Of the three patients with spontaneous echo contrast, two patients developed thrombosis in the left superior vein stump within 3 months after the operation. There was no patient who developed arterial infarction. CONCLUSIONS: In patients who underwent left upper lobectomy, intraoperative ultrasonography to evaluate blood flow and the presence of spontaneous echo contrast in the left superior pulmonary vein stump may be useful to predict thrombosis that may cause arterial infarction.

Method for the validation of immunohistochemical staining using SCID mouse xenografts: expression of CD40 and CD154 in human non-small cell lung cancer.

This report proposes a concept for the standardization of immunohistochemical evaluation. Immunohistochemical staining has several problems associated with the sensitivity of the technical process and standardization of the assessment of potent staining. We provided data focusing on this concept through immunostaining for CD154 in non-small cell lung cancer (NSCLC). We used two types of anti-CD154 antibody as primary antibodies in immunohistochemical staining, as previously reported. Western blot analysis confirmed strong CD154 expression in the cultured cell line PC10, but not in LK2. We also assessed CD154 expression in SCID mouse xenografts of these cell lines. SCID xenograft data on western blot analysis were consistent with those of cultured cell lines. These xenografts could thus be used as positive or negative tissue controls for CD154 immunostaining. Primary antibodies should therefore be confirmed as recognizing target lesions, while control tissue specimens should be objectively confirmed as having target products using another experimental method. Our method would allow results to be unified at more than one laboratory and could act as an objective control assessment method in immunohistochemistry.

The CD40-CD154 interaction would correlate with proliferation and immune escape in pancreatic ductal adenocarcinoma.

BACKGROUND: CD40 and CD154 are associated with lymphocyte signaling pathways and they are also expressed in some malignant neoplasms, but the significance in pancreatic cancer is unknown. METHODS: Eighty pancreatic cancer specimens were stained immunohistochemically, and the results were correlated with the patients' clinicopathologic features. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. RESULT: Immunohistochemical analysis of tumor cells showed that 29 patients (36.3%) were positive for CD40, and 17 patients (21.3%) had very high CD154 expression. The survival of patients who had very high CD154 expression was significantly better than that of others (P = 0.0198). Univariate and multivariate analysis revealed that very high CD154 expression in cancer cells was not an independent, favorable prognostic factor (risk ratio, 0.493; P = 0.0224). On in vitro proliferation assay, the growth of PK-45P and KP-4 cells was blocked by CD40 and CD154 blocking antibodies. Moreover, on in vitro cytokine assay, Th-2 cytokines from PK-45P and SUIT-2 were blocked by CD40 or CD154 blocking antibody. CONCLUSION: These results suggest that the CD40-CD154 interaction would correlate with cell proliferation and secretion of cytokines in PDAC cells, and CD154 overexpression could be a favorable prognostic factor in PDAC patients.

[A case of bisphosphonate-associated osteonecrosis of the jaw in a patient with bone metastasis of breast cancer].

A 5 6-year-old woman underwent modified radical mastectomy for left breast cancer in 2002. Bone metastases developed in November 2005, and she received pamidronate from February 2006. Pamidronate was changed to zoledronate in November 2006. In November 2007, she was referred to a dentist for pain and swelling of the right lower gum. Conservative therapy with local irrigation and antibiotics was performed, but the lesion progressed and showed ulceration with exposed bone. She was diagnosed as bisphosphonate-associated osteonecrosis of the jaws, and zoledronate was withdrawn in January 2008. Conservative therapy was continued but the necrotic lesion caused pathological fracture and fistula. In February 2009, surgical intervention was performed for the improvement of her QOL.

[A case of premenopausal stage IV breast cancer responding to neoadjuvant endocrine therapy after chemotherapy with FEC].

A 33-year-old woman was referred to our hospital with a complaint of left breast tumor. After examinations, she was diagnosed as invasive ductal carcinoma with sternum metastasis (T2N0M1(OSS), Stage IV). The tumor was hormone receptor- positive and HER2-negative. Primary systemic chemotherapy with FEC was performed. After four courses, the efficacy was judged as a partial response (PR). After chemotherapy, endocrine therapy with goserelin and tamoxifen was performed. The efficacy of endocrine therapy was as good as that of chemotherapy. After endocrine therapy for 13 months, breast conserving-surgery was performed. After surgery, radiotherapy for left breast and sternum was performed. She continues to undergo outpatient endocrine therapy with no detectable tumor. It is suggested that neoadjuvant endocrine therapy may be useful with consideration for treatment effectiveness and the patient's quality of life.

[Two cases of breast cancer responding to primary systemic chemotherapy containing trastuzumab without surgery].

The first case was a 40-year-old woman who was referred to our hospital with a complaint of left breast tumor. She was diagnosed as invasive ductal carcinoma (T2N0M0, Stage IIA). The tumor was ER-negative, PR-negative and HER2-positive. After primary systemic chemotherapy with 6 courses of 5-fluorouracil+epirubicin+cyclophosphamide(FEC)and 3 courses of weekly paclitaxel (PTX)+trastuzumab, the efficacy of chemotherapy was judged as a complete response (CR). After chemotherapy, radiotherapy for her left breast was performed without surgery. At 21 months after CR, local efficacy was judged as CR, but liver and bone metastases appeared, and were treated by capecitabine and trastuzumab. The efficacy of chemotherapy was judged as a partial response (PR). The second case was a 26-year-old woman referred to our hospital with a complaint of right breast tumor. She was diagnosed as invasive lobular carcinoma (T2N0M0, Stage IIA). The tumor was ER-positive, PR-negative and HER2-positive. After primary systemic chemotherapy with 4 courses of FEC and 6 courses of docetaxel+trastuzumab, the efficacy of chemotherapy was judged as CR. Then, 4 courses of weekly PTX+trastuzumab were performed. After chemotherapy, radiotherapy for her right breast was performed without surgery. The efficacy of treatment was judged as CR for 15 months.

[A case of stage IV breast cancer with large cancer ulcer responding to combination therapy of capecitabine and medroxyprogesterone acetate and cyclophosphamide].

A 53-year-old woman suffering from nausea and vomiting was admitted to our hospital. There was a large ulcer from her left anterior chest to her right side chest. After pathological examination from the ulcer, she was diagnosed as breast cancer, scirrhous carcinoma. The estrogen and progesterone receptors were positive in the tumor. HER2 score was 1+ in the tumor. The stage was T4bNxM1(OTH). Uterine metastases of the breast cancer caused obstructive nephropathy. Ureteral obstruction was treated by urinary tract catheter. After improvement of renal failure, chemotherapy with 5-FU+epirubicin+cyclophosphamide (FEC) and docetaxel was performed. The efficacy was judged as stable disease (SD). For third-line chemotherapy, she was then treated with oral combination chemoendocrine therapy with capecitabine and medroxyprogesterone acetate. After the combination chemoendocrine therapy, the local tumor was remarkably reduced. With added cyclophosphamide, the partial response (PR) continued for 19 months. She died of peritonitis carcinomatosa and pleuritis carcinomatosa. No adverse reactions occurred with the combination chemoendocrine therapy. It is suggested that this oral combination chemoendocrine therapy may be useful with consideration for treatment effectiveness and the quality of life of the patient.

Adenovirus-mediated eukaryotic initiation factor 4E binding protein-1 in combination with rapamycin inhibits tumor growth of pancreatic ductal adenocarcinoma in vivo.

Over-expression of eIF4E indicates a poor prognosis in different tumors. In the present study, we investigated the frequency of eIF4E, 4E-BP1 and phosphorylated 4E-BP1 expression in PDAC cell lines, gastric carcinoma (GC) cell lines and human embryonic pancreatic cells, as well as gene therapy using translation repressor gene 4E-BP1 in combination with the mTOR inhibitor rapamycin. We also assessed the significance of eIF4E expression in 80 PDAC cases. Combination therapy of adenovirus vector-delivered 4E-BP1 gene and rapamycin was administered to determine their growth inhibition effect in vitro and in vivo in mice. Our study revealed that all PDAC cell lines, GC cell lines and human embryonic pancreas-derived cells expressed the 25-kDa eIF4E protein (MIAPaca-2 cells also expressed the 13-kDa protein 4E-BP1). The 80 PDAC specimens showed a heterogeneous pattern of eIF4E staining. No significant correlation between eIF4E expression and TNM classification was found. Adenovirus vectors Ad-4E-BP1 and Ad-GFP efficiently showed transgenic expression with hyperphosphorylation of 4E-BP1; however, insignificant growth inhibition of the PDAC and GC cell lines was observed. Combination therapy with rapamycin significantly inhibited proliferation and tumor growth in vitro as well as in vivo. Therefore, combination of Ad 4E-BP1 and rapamycin may be a more effective adjuvant therapy.