Periostin in Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression by Enhancing Cancer and Stromal Cell Migration.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are involved in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). CAF-like cells were generated through direct co-culture of human bone marrow-derived mesenchymal stem cells, one of CAF origins, with ESCC cells. Periostin (POSTN) was found to be highly expressed in CAF-like cells. After direct co-culture, ESCC cells showed increased malignant phenotypes, such as survival, growth, and migration, as well as increased phosphorylation of Akt and extracellular signal-regulated kinase (Erk). Recombinant human POSTN activated Akt and Erk signaling pathways in ESCC cells, enhancing survival and migration. The suppression of POSTN in CAF-like cells by siRNA during direct co-culture also suppressed enhanced survival and migration in ESCC cells. In ESCC cells, knockdown of POSTN receptor integrin ß4 inhibited Akt and Erk phosphorylation, and survival and migration increased by POSTN. POSTN also enhanced mesenchymal stem cell and macrophage migration and endowed macrophages with tumor-associated macrophage-like properties. Immunohistochemistry showed that high POSTN expression in the cancer stroma was significantly associated with tumor invasion depth, lymphatic and blood vessel invasion, higher pathologic stage, CAF marker expression, and infiltrating tumor-associated macrophage numbers. Moreover, patients with ESCC with high POSTN expression exhibited poor postoperative outcomes. Thus, CAF-secreted POSTN contributed to tumor microenvironment development. These results indicate that POSTN may be a novel therapeutic target for ESCC.

Pseudoimmunofluorescent immunohistochemistry image analysis of phosphorylated signaling proteins in human esophageal squamous cell carcinoma tissue.

Immunohistochemistry is primarily employed to visualize the localization of specific molecules in tissue samples. However, there is an increasing need for software-assisted quantitative assessment. In the present study, we performed inverted blue channel-based pseudoimmunofluorescence image analysis using original immunohistochemistry images. In human esophageal squamous cell carcinoma tissues, various humoral factors promote the phosphorylation of signaling proteins, including protein kinase B (Akt) and/or extracellular signal-regulated kinase 1/2 (ERK1/2), leading to tumor progression. Our method demonstrated applicability in the analysis of localized signaling proteins in histological sections. Relatively high phosphorylated Akt (p-Akt) intensity was observed in the cancer-stroma adjacent (Adj) and noncancerous regions of the superficial layer (SL). Furthermore, localized phosphorylated ERK1/2 (Thr202/Tyr204) was observed in the Adj of the SL and invasive front, distinct from the pattern of p-Akt (Ser473) and p-Akt (Thr308). In conclusion, pseudoimmunofluorescent immunohistochemistry image analysis is useful for the quantitative assessment and objective interpretation of localized signaling proteins in esophageal squamous cell carcinoma. The method can also be applied to analyze various immunohistochemistry images from diverse tissues.

Colostomy-site carcinoma with primitive phenotype in a rectal cancer patient after achieving pathological complete response with neoadjuvant chemoradiotherapy.

Herein, we report a rare case of a carcinoma with primitive phenotype (enteroblastic and/or hepatoid differentiation) occurring at a colostomy site. The patient was an elderly male who underwent neoadjuvant chemoradiotherapy for rectal cancer, followed by abdominoperineal resection. A biopsy specimen for the rectal carcinoma before neoadjuvant chemoradiotherapy was conventional tubular adenocarcinoma. Moreover, a pathological complete response was confirmed in the proctectomy specimen. However, a colostomy-site tumor appeared 6 months after the proctectomy, and it was resected 1 year after the initial proctectomy. The colostomy-site tumor comprised solid to focal glandular growth of atypical polygonal cells with clear to pale eosinophilic cytoplasm and was immunohistochemically positive for cytokeratin, spalt-like transcription factor 4, glypican-3, caudal type homeobox 2, and special AT-rich sequence-binding protein 2. Thus, the tumor was diagnosed as poorly differentiated adenocarcinoma with primitive phenotype, with suggested origin from the colorectal epithelium. Additionally, a multilocular cystic lesion comprising various types of epithelia was found adjacent to the tumor, suggestive of metaplasia or heterotopia. Changes in the histology and immunophenotype, and the findings of an adjacent cystic lesion suggest a metachronous tumor rather than a recurrence of the primary tumor.

IFI16 Induced by Direct Interaction between Esophageal Squamous Cell Carcinomas and Macrophages Promotes Tumor Progression via Secretion of IL-1α.

Tumor-associated macrophages (TAMs), one of the major components of the tumor microenvironment, contribute to the progression of esophageal squamous cell carcinoma (ESCC). We previously established a direct co-culture system of human ESCC cells and macrophages and reported the promotion of malignant phenotypes, such as survival, growth, and migration, in ESCC cells. These findings suggested that direct interactions between cancer cells and macrophages contribute to the malignancy of ESCC, but its underlying mechanisms remain unclear. In this study, we compared the expression levels of the interferon-induced genes between mono- and co-cultured ESCC cells using a cDNA microarray and found that interferon-inducible protein 16 (IFI16) was most significantly upregulated in co-cultured ESCC cells. IFI16 knockdown suppressed malignant phenotypes and also decreased the secretion of interleukin-1α (IL-1α) from ESCC cells. Additionally, recombinant IL-1α enhanced malignant phenotypes of ESCC cells through the Erk and NF-κB signaling. Immunohistochemistry revealed that high IFI16 expression in human ESCC tissues tended to be associated with disease-free survival and was significantly associated with tumor depth, lymph node metastasis, and macrophage infiltration. The results of this study reveal that IFI16 is involved in ESCC progression via IL-1α and imply the potential of IFI16 as a novel prognostic factor for ESCC.

Biological and clinical significance of the YKL-40/osteopontin-integrin ß4-p70S6K axis induced by macrophages in early oesophageal squamous cell carcinoma.

M2 macrophages contribute to the progression of oesophageal squamous cell carcinoma (ESCC); however, the roles of M2 macrophages in early ESCC remain unclear. To clarify the biological mechanisms underlying the interaction between M2 macrophages and oesophageal epithelial cells in early-stage ESCC, in vitro co-culture assays between the immortalised oesophageal epithelial cell line Het-1A and cytokine-defined M2 macrophages were established. Co-culture with M2 macrophages promoted the proliferation and migration of Het-1A cells via the mTOR-p70S6K signalling pathway activated by YKL-40, also known as chitinase 3-like 1, and osteopontin (OPN) that were hypersecreted in the co-culture supernatants. YKL-40 and OPN promoted the above phenotypes of Het-1A by making a complex with integrin ß4 (ß4). Furthermore, YKL-40 and OPN promoted M2 polarisation, proliferation, and migration of macrophages. To validate the pathological and clinical significances of in vitro experimental results, immunohistochemistry of human early ESCC tissues obtained by endoscopic submucosal dissection (ESD) was performed, confirming the activation of the YKL-40/OPN-ß4-p70S6K axis in the tumour area. Moreover, epithelial expression of ß4 and the number of epithelial and stromal infiltrating YKL-40- and OPN-positive cells correlated with the Lugol-voiding lesions (LVLs), a well-known predictor of the incidence of metachronous ESCC. Furthermore, the combination of high expression of ß4 and LVLs or high numbers of epithelial and stromal infiltrating YKL-40- and OPN-positive immune cells could more clearly detect the incidence of metachronous ESCC than each of the parameters alone. Our results demonstrated that the YKL-40/OPN-ß4-p70S6K axis played important roles in early-stage ESCC, and the high expression levels of ß4 and high numbers of infiltrating YKL-40- and OPN-positive immune cells could be useful predictive parameters for the incidence of metachronous ESCC after ESD. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Matrix Metalloproteinase 9 Induced in Esophageal Squamous Cell Carcinoma Cells via Close Contact with Tumor-Associated Macrophages Contributes to Cancer Progression and Poor Prognosis.

Tumor-associated macrophages (TAMs) contribute to disease progression in various cancers, including esophageal squamous cell carcinoma (ESCC). We have previously used an indirect co-culture system between ESCC cell lines and macrophages to analyze their interactions. Recently, we established a direct co-culture system to closely simulate actual ESCC cell-TAM contact. We found that matrix metalloproteinase 9 (MMP9) was induced in ESCC cells by direct co-culture with TAMs, not by indirect co-culture. MMP9 was associated with ESCC cell migration and invasion, and its expression was controlled by the Stat3 signaling pathway in vitro. Immunohistochemical analyses revealed that MMP9 expression in cancer cells at the invasive front ("cancer cell MMP9") was related to high infiltration of CD204 positive M2-like TAMs (p < 0.001) and was associated with worse overall and disease-free survival of patients (p = 0.036 and p = 0.038, respectively). Furthermore, cancer cell MMP9 was an independent prognostic factor for disease-free survival. Notably, MMP9 expression in cancer stroma was not associated with any clinicopathological factors or patient prognoses. Our results suggest that close interaction with TAMs infiltrating in cancer stroma or cancer nests induces MMP9 expression in ESCC cells, equipping them with more malignant features.

Roles of IL-7R Induced by Interactions between Cancer Cells and Macrophages in the Progression of Esophageal Squamous Cell Carcinoma.

High infiltration of tumor-associated macrophages (TAMs), which contribute to the progression of several cancer types, is correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). In addition to the previously reported increase in migration and invasion, ESCC cells co-cultured directly with macrophages exhibited enhanced survival and growth. Furthermore, interleukin-related molecules are associated with ESCC; however, the precise mechanism underlying this association is unclear. Therefore, we explored the role of interleukin-related molecules in ESCC progression. A cDNA microarray analysis of monocultured and co-cultured ESCC cells revealed that the interleukin 7 receptor (IL-7R) was upregulated in ESCC cells co-cultured with macrophages. Overexpression of IL-7R promoted the survival and growth of ESCC cells by activating the Akt and Erk1/2 signaling pathways. The IL-7/IL-7R axis also contributed to the promotion of ESCC cell migration via the Akt and Erk1/2 signaling pathways. Furthermore, immunohistochemistry showed that ESCC patients with high IL-7R expression in cancer nests exhibited a trend toward poor prognosis in terms of disease-free survival, and showed significant correlation with increased numbers of infiltrating macrophages and cancer-associated fibroblasts. Therefore, IL-7R, which is upregulated when directly co-cultured with macrophages, may contribute to ESCC progression by promoting the development of various malignant phenotypes in cancer cells.

Postmortem Diagnosis of Gallbladder Cancer Presenting as Pulmonary Lymphangitic Carcinomatosis With Concurrent Gallbladder Adenomyomatosis.

In pulmonary lymphangitic carcinomatosis, it can be difficult to identify the primary site of the cancer on computed tomography (CT) imaging. Here, we report a rare case of pulmonary lymphangitic carcinomatosis, which was difficult to diagnose as gallbladder cancer. An 81-year-old woman, previously followed up for gallbladder adenomyomatosis, presented with persistent cough. CT revealed multiple small nodular opacities, irregular interlobular septal thickening, and bilateral pleural effusions. Based on the CT findings and the presence of malignant cells in the pleural fluid, a presumptive diagnosis of pulmonary lymphangitic carcinomatosis was made, but the primary site was not identified. The patient died of respiratory failure in two months. Autopsy confirmed gallbladder cancer with pulmonary lymphangitic carcinomatosis and multiorgan metastasis. Clinicians should be aware that in patients with gallbladder adenomyomatosis, gallbladder cancer can present with rapidly progressive respiratory symptoms even in the absence of an evident mass or increased gallbladder wall thickening.

Chronological analysis of the gut microbiome for efficacy of atezolizumab-based immunotherapy in non-small cell lung cancer: Protocol for a multicenter prospective observational study.

BACKGROUND: Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is an innovative treatment for non-small cell lung cancer (NSCLC). Recently, the specific composition of the gut microbiome before initiation of cancer immunotherapy has been highlighted as a predictive biomarker in patients undergoing cancer immunotherapy, mainly in the US or Europe. However, the fact gut microbiome status is completely different in races or countries has been revealed. In addition, how the microbiome composition and diversity chronologically change during cancer immunotherapy is still unclear. METHODS: This multicenter, prospective observational study will analyze the association between the gut microbiome and therapeutic response in NSCLC patients who received atezolizumab-based immunotherapy. The aim of the present study is to clarify not only how the specific composition of the gut microbiome influences clinical response in NSCLC patients but the chronological changes of gut microbiota during atezolizumab-based immunotherapy. The gut microbiota will be analyzed using 16S rRNA gene sequencing. The main inclusion criteria are as follows: (1) Pathologically- or cytologically-confirmed stage IV or postoperative recurrent NSCLC. (2) Patients ≥20 years old at the time of informed consent. (3) Planned to treat with atezolizumab-based immunotherapy combined with platinum-based chemotherapy (cohort 1) and monotherapy (cohort 2) as a first immunotherapy. (4) Patients to provide fecal samples. A total of 60 patients will be enrolled prospectively. Enrollment will begin in 2020 and the final analyses will be completed by 2024. DISCUSSION: This trial will provide more evidence of how gut microbiota composition and diversity chronologically change during cancer immunotherapy and contribute to the development of biomarkers to predict ICI response as well as biotic therapies which enhance the ICI response.

S100A8/A9 Induced by Interaction with Macrophages in Esophageal Squamous Cell Carcinoma Promotes the Migration and Invasion of Cancer Cells via Akt and p38 MAPK Pathways.

Tumor-associated macrophages are associated with more malignant phenotypes of esophageal squamous cell carcinoma (ESCC) cells. Previously, an indirect co-culture assay of ESCC cells and macrophages was used to identify several factors associated with ESCC progression. Herein, a direct co-culture assay of ESCC cells and macrophages was established, which more closely simulated the actual cancer microenvironment. Direct co-cultured ESCC cells had significantly increased migration and invasion abilities, and phosphorylation levels of Akt and p38 mitogen-activated protein kinase (MAPK) compared with monocultured ESCC cells. According to a cDNA microarray analysis between monocultured and co-cultured ESCC cells, both the expression and release of S100 calcium binding protein A8 and A9 (S100A8 and S100A9), which commonly exist and function as a heterodimer (herein, S100A8/A9), were significantly enhanced in co-cultured ESCC cells. The addition of recombinant human S100A8/A9 protein induced migration and invasion of ESCC cells via Akt and p38 MAPK signaling. Both S100A8 and S100A9 silencing suppressed migration, invasion, and phosphorylation of Akt and p38 MAPK in co-cultured ESCC cells. Moreover, ESCC patients with high S100A8/A9 expression exhibited significantly shorter disease-free survival (P = 0.005) and cause-specific survival (P = 0.038). These results suggest that S100A8/A9 expression and release in ESCC cells are enhanced by direct co-culture with macrophages and that S100A8/A9 promotes ESCC progression via Akt and p38 MAPK signaling pathways.

Metallothionein 2A Expression in Cancer-Associated Fibroblasts and Cancer Cells Promotes Esophageal Squamous Cell Carcinoma Progression.

Esophageal cancer has the sixth highest mortality rate worldwide. Cancer-associated fibroblasts (CAFs) are involved in the progression of various cancers. Previously, we demonstrated an association between high expression of the CAF marker, fibroblast activation protein, and poor prognosis of esophageal squamous cell carcinoma (ESCC). We also established CAF-like cells by indirect co-culture of bone marrow-derived mesenchymal stem cells with ESCC cell lines and found metallothionein 2A (MT2A) to be highly expressed in them. Here, to explore the function of MT2A in CAFs, we silenced MT2A in the CAF-like cells and ESCC cell lines using small interfering RNA. MT2A knockdown in the CAF-like cells suppressed expression and secretion of insulin-like growth factor binding protein 2 (IGFBP2); recombinant IGFBP2 promoted migration and invasiveness of ESCC cells via NFκB, Akt, and Erk signaling pathways. Furthermore, MT2A knockdown in the ESCC cell lines inhibited their growth, migration, and invasiveness. Immunohistochemistry demonstrated that high MT2A expression in the cancer stroma and cancer nest of ESCC tissues correlated with poor prognosis of ESCC patients. Hence, we report that MT2A in CAFs and cancer cells contributes to ESCC progression. MT2A and IGFBP2 are potential novel therapeutic targets in ESCC.

First-line osimertinib for leptomeningeal metastasis from lung adenocarcinoma with EGFR mutation as the initial and solitary site of postoperative recurrence.

Leptomeningeal metastasis (LM) from lung cancer has poor prognosis, and effective therapy has not been established. We present the case of a 54-year-old man with LM from lung adenocarcinoma harboring EGFR L858R point mutation, who received osimertinib as first-line therapy. He had previously undergone left lower lobectomy and lymph node dissection for lung adenocarcinoma. Five years and 9 months after the operation, he developed symptoms of dizziness, lightheadedness, and headache. Magnetic resonance imaging showed high signal intensity in the cerebral sulcus and meninges, and cerebrospinal fluid (CSF) cytology indicated adenocarcinoma with EGFR L858R point mutation, which suggested LM. After CSF drainage and administration of corticosteroid and glycerol, the patient received osimertinib (80 mg/day) as first-line therapy. These symptoms including dizziness, lightheadedness, and headache were relieved and the MRI appearance was normal, and he survived for 19 months with no disease progression. Osimertinib is considered to be an effective therapeutic option for LM from lung adenocarcinoma harboring EGFR mutation.

A phase II randomized trial of adjuvant chemotherapy with S-1 versus S-1 plus cisplatin for completely resected pathological stage II/IIIA non-small cell lung cancer.

OBJECTIVES: Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC. PATIENTS AND METHODS: We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7th TNM classification) who underwent complete resection from 2009 to 2013. The primary endpoint, the 2-year disease-free survival (DFS) rate, was evaluated using the Bayesian method. Eligible patients were randomly assigned to two arms: oral S-1 monotherapy (S-1 arm) and S-1 plus cisplatin combination therapy followed by S-1 (S-1 plus cisplatin arm) both for a total of 1 year. RESULTS: A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P = 0.1695 and P = 0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%). CONCLUSIONS: Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience.

A feasibility trial of postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for elderly patients with non-small cell lung cancer: a report of the Lung Oncology Group in Kyushu (LOGIK) protocol 0901.

BACKGROUND: The present study was designed to determine whether adjuvant chemotherapy with S-1 after surgical resection is feasible in elderly patients with non-small cell lung cancer (NSCLC), using a multi-institutional trial. METHODS: From July 2009 to July 2011, 25 patients received the following regimen: 2 weeks of administration and 1 week of withdrawal of S-1 at 50-100 mg/body per day in an outpatient setting. The primary endpoint of this trial was the completion rate of eight cycles. RESULTS: The completion rate of eight cycles was 70.8 % [95 % confidence interval (CI) 52.7-89.0 %]. The perfect completion rate of eight cycles on schedule with full doses without delays was 50 % (95 % CI 30.0-70.0 %). The reasons for incomplete cycles were: patient refusal in four cases, anorexia in two cases and thrombocytopenia in one case. As a consequence of delays and/or dose reductions, the relative dose intensity of S-1 was 76.3 %. CONCLUSIONS: Adjuvant chemotherapy with S-1 at a reduced dose and schedule was therefore found to be a feasible treatment for elderly Japanese patients who had undergone surgical resection for NSCLC (UMIN Clinical Trials Registry number UMIN000002383).

Repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma associated with chronic hepatitis C: report of a case.

We report a case of repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma (HCC). A 75-year-old man with chronic hepatitis C underwent partial hepatectomy for a 25 mm hepatic tumor in S5. The histological diagnosis was diffuse large B-cell malignant lymphoma and as postoperative (18)F-fluorodeoxyglucose-positron emission tomography showed no hot spots, the mass was presumed to be primary hepatic lymphoma. Thus, adjuvant systemic chemotherapy was given following the hepatectomy. Abdominal ultrasonography, done 12 months after the hepatectomy, showed a hepatic tumor in S6 and repeat partial hepatectomy was performed. This tumor was histologically diagnosed as HCC.

Large simple hepatic cysts leading to gastric fundal varices in a noncirrhotic patient.

A 74-year-old noncirrhotic woman presented with abdominal distension and pain in the right hypochondrium. Contrast-enhanced computed tomography (CT) demonstrated multiple large simple liver cysts occupying the right lobe of the liver, the largest of which was 19 cm in diameter. Gastric varices were enhanced in the fundus of the stomach. The patient underwent surgery to deroof the hepatic cysts with ablation using argon beam coagulation. Esophagogastroduodenoscopy (EGD) showed that the portal hypertensive gastropathy was ameliorated after the operation; however, the fundal varices were only slightly decreased. After the operation, we observed that the hepatic vein waveform gradually changed from a gently curved pattern to a normal triphasic pattern. We treated the fundal varices with balloon-occluded retrograde transvenous obliteration 3 months after the initial operation. We describe our successful treatment of this rare case and discuss the utility of hepatic vein waveform analysis in the study of portal hypertension.

Incidence and predictors of deep venous thrombosis after abdominal oncologic surgery: prospective Doppler ultrasound screening.

BACKGROUND: Venous thromboembolism is a relatively rare but serious complication of abdominal surgery. This study evaluated the incidence and risk factors for the development of deep venous thrombosis (DVT) after abdominal oncologic surgery using color Doppler ultrasonography (DUS). METHODS: This study enrolled 132 consecutive patients who underwent elective abdominal surgery for malignant tumors. Patients were investigated for DVT using DUS on postoperative day 7 ± 2. Correlations between the incidence of DVT and clinicopathologic parameters and the postoperative course were evaluated. RESULTS: DVT was found in 15 patients (11.4%) using DUS. Clinically evident venous thromboembolism, including pulmonary embolism, was not found in these patients. The incidence of DVT was significantly higher in females (P=0.002), patients with a lower body mass index (P=0.008), and patients with a higher preoperative D-dimer level (P<0.0001). CONCLUSIONS: DUS is noninvasive and is useful for postoperative DVT screening. Thromboprophylaxis is essential in high-risk patients who have undergone abdominal oncologic surgery.

Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma: prognostic impact of the preoperative serum alpha-fetoprotein level.

PURPOSE: Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors. METHODS: This study retrospectively reviewed 20 patients who underwent pulmonary metastasectomy from an HCC between 1990 and 2007 at two institutions. The surgical outcome was evaluated by both the overall survival and cancer-specific survival after pulmonary resection. The association between various clinico-pathological factors and the survival outcome was analyzed. RESULTS: The overall survival rate after the initial pulmonary metastasectomy was 46.9% at 5 years, and the cancer-specific 5-year survival rate was 63.2%. One patient died of surgery-related events 19 days after the pulmonary resection. The preoperative AFP (alpha-fetoprotein) level was found to be a significant prognostic factor for both overall and cancer-specific survival for patients undergoing pulmonary metastasectomy. Both the overall and cancer-specific survival rates were significantly worse for the patients with AFP ≥ 500 ng/ml in comparison to those with AFP < 500 ng/ml (p < 0.05). No other factors were associated with the survival after pulmonary metastasectomy. CONCLUSION: The serum level of AFP might be a valuable predictor for the outcome of pulmonary metastasectomy required for metastasis of HCC.

Surgical treatment of stage IV non-small cell lung cancer.

Most stage IV non-small-cell lung cancer (NSCLC) patients are not amenable to curative treatment. The purpose of this study was to analyse our initial experience with an aggressive surgical strategy for stage IV NSCLC, and to define which patients can benefit from this treatment. Forty-six stage IV NSCLC patients who underwent surgical resection of both primary lung cancer and metastatic sites from April 1989 to December 2010 were included in this study. The record of each patient was reviewed for age, gender, pN status, sites of metastasis, histology, surgical procedure and duration of survival. There were 13 females and 33 males. Their median age was 62.0 years (range, 44-82 years). The overall 5-year survival rate was 23.3% (median, 20.0 months), and the disease-free survival rate was 15.8% at 5 years (median, 16.1 months). Patients with the pN2 status had a significantly worse survival than patients with a pN0 or pN1 status (8.6 versus 33.1%, P = 0.0497). According to a multivariate Cox proportional hazards analysis, no independent predictor of survival was identified. The results of our study suggest that surgical treatment can extend the survival in stage IV NSCLC patients if the patients can tolerate surgery.

Prediction of the prognosis and surgical indications for pulmonary metastectomy from colorectal carcinoma in patients with combined hepatic metastases.

BACKGROUND: The value of surgical treatment for patients with pulmonary and hepatic metastases from colorectal carcinoma is controversial. The purpose of this study was to analyze our initial experience with this aggressive strategy, and to define the prognosis and the surgical indications. METHODS: The records of 35 patients who underwent surgical treatments for both hepatic and pulmonary metastases from colorectal carcinoma, from January 1997 to December 2008, were retrospectively analyzed. RESULTS: There were 18 females and 17 males with a median age was 62.0 years. The primary colorectal neoplasm was located at the colon in 23 patients (65.7%) and in the rectum in 12 patients (34.3%). The overall 5-year and 10-year survival rates were 65.3% and 31.5% from the date of primary colorectal resection, respectively. For patients who underwent metachronous hepatic and pulmonary surgical treatment, the 10-year survival rate was 40.9%, which was significantly better than that of those undergoing synchronous hepatic and pulmonary surgical treatment (p=0.0265). Patients who have pulmonary less than ten of metastasis thus seemed to have a better prognosis than those with more than ten, but the difference was quite significant (p=0.0719). In a multivariate Cox proportional hazards model, synchronous hepatic and pulmonary metastases was identified as an independent predictor of adverse survival (p=0.0073). CONCLUSIONS: The results of our study suggest that hepatic and pulmonary surgical treatment can provide a better prognosis for patients with metachronous hepatic and pulmonary metastases from colorectal carcinoma. We believe that aggressive metastasectomy can be an option for selected patients, even if a patient has been previously treated for hepatic and pulmonary metastases from colorectal carcinoma.