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This work examined the effect of changing molding conditions on the physical aging of polystyrene injection moldings. First, we investigated the relationship between the molecular orientation and the molding conditions. The molecular orientation near the surface changed with changing injection rate, so we hypothesized that this molecular orientation might form during the filling stage. Because this molecular orientation did not relax under heat treatment below the glass transition temperature (T g), the oriented molecules near the surface were thought to be elongated owing to the high strain rate during the filling stage. On the other hand, the molecular orientation in the core layer changed with changing holding pressure and relaxed under heat treatment below T g. Thus, the molecules in the core layer might become oriented during the holding stage and not be elongated owing to the slow strain rate. Furthermore, the molecular orientation in the core layer decreased with increasing mold temperature, and the physical heat resistance improved with increasing mold temperature. Meanwhile, the excess enthalpy did not change with changing molding conditions. Therefore, the improvement in physical heat resistance with increasing mold temperature was likely caused by the decrease in the molecular orientation in the core layer. Analyzing the relaxation behavior of the molecular orientation suggested that increasing mold temperature reduced the number of oriented molecules with large deformation in the core layer.

The treatment strategies for colorectal cancer (CRC) must ensure a radical cure of cancer and prevent over/under treatment. Biopsy specimens used for the definitive diagnosis of T1 CRC were analyzed using artificial intelligence (AI) to construct a risk index for lymph node metastasis.A total of 146 T1 CRC cases were analyzed. The specimens for analysis were mainly biopsy specimens, and in the absence of biopsy specimens, the mucosal layer of the surgical specimens was analyzed. The pathology slides for each case were digitally imaged, and the morphological features of cancer cell nuclei were extracted from the tissue images. First, statistical methods were used to analyze how well these features could predict lymph node metastasis risk. A lymph node metastasis risk model using AI was created based on these morphological features, and accuracy in test cases was verified.Each developed model could predict lymph node metastasis risk with a 90% accuracy in each region of interest of the training cases. Lymph node metastasis risk was predicted with 81.8-86.3% accuracy for randomly validated cases, using a learning model with biopsy data. Moreover, no case with lymph node metastasis or lymph node risk was judged to have no risk using the same model.AI models suggest an association between biopsy specimens and lymph node metastases in T1 CRC and may contribute to increased accuracy of preoperative diagnosis.

Black thyroid is characterized by a rare pigment change observed almost exclusively in patients taking minocycline. We present the case of a 72-year-old man diagnosed with T3N3bM0 stage IVB hypopharyngeal squamous cell carcinoma who had been taking minocycline for approximately 18 months as a treatment for prurigo chronica multiformis. Initial treatment consisted of total pharyngolaryngoesophagectomy, bilateral neck dissection, total thyroidectomy, pharyngeal reconstruction using a free jejunal autograft, and creation of a permanent tracheostoma. During surgery, black discoloration of the thyroid and trachea was observed. Postoperative histological findings confirmed the black discoloration, with deposits of dark-brown, melanin-like granules observed in the thyroid, trachea, thyroid cartilage, and cricoid cartilage. Therefore, the black discoloration of the thyroid associated with the use of minocycline can extend to the thyroid cartilage, cricoid cartilage, and trachea. This information is important for surgeons to recognize in order to prevent unnecessary resection due to misdiagnosis.

Mitochondria are key cytoplasmic organelles. Their activation is critical for the generation of T cell proliferation and cytotoxicity. Exhausted tumor‐infiltrating T cells show a decreased mitochondrial function and mass. 5‐Aminolevulinic acid (5‐ALA), a natural amino acid that is only produced in the mitochondria, has been shown to influence metabolic functions. We hypothesized that 5‐ALA with sodium ferrous citrate (SFC) might provide metabolic support for tumor‐infiltrating T cells. In a mouse melanoma model, we found that 5‐ALA/SFC with a programmed cell death‐ligand 1 (PD‐L1) blocking Ab synergized tumor regression. After treatment with 5‐ALA/SFC and anti‐PD‐L1 Ab, tumor infiltrating lymphocytes (TILs) were not only competent for the production of cytolytic particles and cytokines (granzyme B, interleukin‐2, and γ‐interferon) but also showed enhanced Ki‐67 activity (a proliferation marker). The number of activated T cells (PD‐1+Tim‐3−) was also significantly increased. Furthermore, we found that 5‐ALA/SFC activated the mitochondrial functions, including the oxygen consumption rate, ATP level, and complex V expression. The mRNA levels of Nrf‐2, HO‐1, Sirt‐1, and PGC‐1α and the protein levels of Sirt‐1 were upregulated by treatment with 5‐ALA/SFC. Taken together, our findings revealed that 5‐ALA/SFC could be a key metabolic regulator in exhausted T cell metabolism and suggested that 5‐ALA/SFC might synergize with anti‐PD‐1/PD‐L1 therapy to boost the intratumoral efficacy of tumor‐specific T cells. Our study not only revealed a new aspect of immune metabolism, but also paved the way to develop a strategy for combined anti‐PD‐1/PD‐L1 cancer immunotherapy., Exhausted T cells have decreased effector and proliferation function. We found that the mRNA levels of the Nrf‐2, HO‐1, Sirt‐1, and PGC‐1α and the protein levels of Sirt‐1 were upregulated by treatment with 5‐aminolevulinic acid (5‐ALA)/sodium ferrous ion (SFC). The enforced expression of PGC‐1α in activated T cells rescued their effector function and enhanced the efficacy of the mitochondrial function. Our findings revealed that 5‐ALA/SFC could be a key metabolic regulator in exhausted T cell metabolism and suggested that 5‐ALA/SFC might synergize with anti‐programmed cell death‐1/programmed cell death‐ligand 1 therapy to boost the intratumoral efficacy of tumor‐specific T cells. ​

In the tumor microenvironment (TME), one of the major functions of tumor-recruited CD11b

Background/aim The tumor microenvironment (TME) balances tumor growth and suppression through humoral factors and cell-cell interactions. In oral squamous cell carcinoma (OSCC), TMEs have been associated with prognosis of cancer patients and are evaluated by microscopy; however, these methods of evaluation vary among studies. Materials and methods To evaluate the TME, borderline microenvironment fibrosis (bMF) was evaluated histologically in 236 OSCC cases and used to determine the clinicopathological status. Results bMF was observed in 47% (110 in 236 cases) of OSCC cases and associated with higher T category, N category, stage, histological grade and mode of invasion. bMF-positive was related to overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that bMF-positive was an independent factor for OS in all cases [n=226; HR=1.683 (1.018-2.781); p=0.042], especially in T1+T2 cases [n=186; HR=1.926 (1.079-3.440); p=0.024], and PFS in all cases [n=226; HR=2.254 (1.397-3.637); p=0.001]. Conclusion bMF may act as a novel biomarker for OSCC.

Lymph node metastasis from signet ring cellcarcinoma (SRCC) primary unknown is extremely rare. We here report a case of primary-unknown SRCC that metastasized to the cervical lymph nodes, co-existing with mucoepidermoid carcinoma (MEC) of the parotid gland as a simultaneous double cancer. A 68-year-old female patient with right swollen cervical lymph nodes consulted our medical center. A diagnosis of bilateral cervical lymph node metastasis and a right parotid tumor was made. After bilateral neck dissection and right parotidectomy, the pathological diagnosis was SRCC of primary unknown with metastasis to the cervical lymph node and MEC of the parotid gland. Examination of the CRTC1/3-MAML2 fusion gene showed no relation between SRCC of primary unknown with metastasis to the cervical lymph node and MEC of the parotid gland. Ten months after the first treatment, there was recurrence in the left neck lymph node, and left neck dissection was performed. Fourteen months after the first treatment, the patient is alive and cancer-free. This case is the fourth report of SRCC with lymph node metastasis, and highlights the value of fusion gene detection to determine relatedness between simultaneous cancers. Moreover, such cases should be closely monitored for the subsequent appearance of distant metastases.

Background: Morbidity following pancreaticoduodenectomy (PD) has been reported to remain high. This study sought to measure the peak Hounsfield units (HUs) of visceral attenuation in patients undergoing PD and to assess the quality of adipocytes by comparing these measurements with perioperative factors. Methods: Patients undergoing PD were retrospectively identified (n = 108). Abdominal perimeter, subcutaneous fat area (SFA), visceral fat area (VFA), and peak HU of the VFA were measured. Logistic regression analysis was used to identify independent predictors of postoperative pancreatic fistula (POPF) or complications. Histopathological examination was performed for qualitative diagnosis of the stromal tissue. Results: The overall rate of POPF was 16%, and severe complications occurred in 23% of the cases. A criterion for peak HU of the VFA only independently predicted POPF (p = 0.007) in the multivariate analysis. A criterion for peak HU of the VFA (p = 0.015) was associated with an increased rate of postoperative severe complications in the univariate analysis. The peak HU of the VFA was significantly correlated with abdominal perimeter (p < 0.001) and VFA (p < 0.001). The peak HU of the VFA was significantly correlated with adipocyte diameter (p < 0.001) and the ratio of stromal connective tissue area around the adipocytes (p < 0.001). Conclusion: The peak HU of the VFA was an independent factor contributing to severe complications, including POPF after PD. It reflects the amount of stromal connective tissue around the adipocytes.

A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly and lymphadenopathy were observed, and development of prominent anasarca and worsening of renal function yielded the diagnosis of TAFRO syndrome. He was treated with high-dose steroids and plasmapheresis, and a thrombopoietin receptor agonist was administered for refractory thrombocytopenia. However, his general condition worsened, and he died on day 92. Histopathological analysis of a kidney autopsy specimen showed thrombotic microangiopathy characterized by glomerular endothelial swelling, mesangiolysis, and double contours of the glomerular capillary walls. His bone marrow showed megakaryocytic hyperplasia with mild reticulin fibrosis. Interestingly, these clinical and pathological features were remarkably similar to those the patient demonstrated before the kidney transplant, suggesting the recurrence of TAFRO syndrome. TAFRO syndrome is a rare systemic disorder whose concept has recently been established, but information on its long-term outcome is scarce. To our knowledge, this is the first case of TAFRO syndrome developing in a kidney transplant recipient, which suggests that disease recurrence occurs many years after the kidney transplant.

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naive and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor. Therefore, it is essential to maintain and enhance the anti-tumoral activity of TADCs to aid tumor elimination. This study demonstrated the potential for tumor growth inhibition of Aureobasidium pullulan-derived β-glucan (AP-BG). Administration of AP-BG dramatically limited the development of different types of tumor cell lines transplanted into mice. Examination of the tumor-infiltrating leukocytes revealed that AP-BG caused high expression of co-stimulatory molecules on TADCs and enhanced the production of cytolytic granules as well as pro-inflammatory cytokines by the tumor-resident T cells. Furthermore, the syngeneic mixed lymphoid reaction assay and popliteal lymph node assay showed the significant ability of AP-BG to improve DCs' antigen-specific priming of T cells in vitro and in vivo. Taken together, β-glucan might be an immune-potentiating adjuvant for cancer treatment. This highly widely-used reagent will initiate a new way to activate DC-targeted cancer immune therapy.

Aims Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). Methods and results We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. Conclusion The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

Background Idiopathic portal hypertension (IPH) generally has a good prognosis and rarely results in liver transplantation. Furthermore, there are few reports of living donor liver transplantation (LDLT) for IPH with extrahepatic portal vein stenosis. Case presentation We report the case of a 51-year-old female patient diagnosed with IPH more than 20 years ago. She suffered severe jaundice, massive ascites, and encephalopathy at the time of her visit to our hospital. The patient’s extrahepatic portal vein showed a scar-like stenosis, and the portal flow was completely hepatofugal. Collateral circulation such as the splenorenal shunt was well developed, and multiple splenic artery aneurysms up to 2 cm were observed in the splenic hilum. Her Model for End-Stage Liver Disease score increased to over 40 because of renal dysfunction, requiring temporary dialysis. We performed LDLT using her husband’s right lobe graft and splenectomy. The extrahepatic stenotic portal vein was completely resected, and the superficial femoral vein (SFV) graft collected from the recipient’s right leg was used for portal reconstruction as an interposition graft. Although the clinical course after LDLT had many complications, the patient was discharged on postoperative day 113 and has been fine for 2 years after LDLT. Histopathologically, the explanted liver had obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal cirrhosis. Conclusion This case showed that severe IPH is occasionally associated with extrahepatic portal vein stenosis and can be treated with LDLT with portal vein reconstruction using an interposition graft. It was also suggested that the SFV is a useful choice for the interposition graft.

Nivolumab administration to patients with organ transplantation history requires careful management. Herein, we report the case of a living-donor liver-transplant recipient, a 52-year-old man, with recurrent and metastatic hypopharyngeal cancer treated with nivolumab. He was diagnosed with T2N2bM0 stage IVA hypopharyngeal squamous cell carcinoma. While using oral immunosuppressants (cyclosporine and mycophenolate mofetil), the patient underwent right neck dissection followed by radiotherapy as an initial treatment. Three months after radiotherapy, positron emission tomography scans revealed multiple bone metastases. We administered two courses of the EXTREME regimen, comprising cisplatin, 5-fluorouracil, and cetuximab, as the first-line treatment for distal metastasis, but the patient presented with progressive disease. The patient was administered nivolumab as the second-line treatment. The programmed death-ligand 1 (PD-L1) expression level in a biopsy specimen of the primary hypopharyngeal tumor and resected specimen of the cervical lymph node metastasis was 40% and 10%, respectively. PD-L1 expression was not detected in hepatocytes of the liver biopsy sample obtained before nivolumab introduction. The patient received four courses of nivolumab 240 mg. Although liver dysfunction was alleviated by adjusting the dose of the hepatoprotective agent and cyclosporine, the progressive disease status persisted after completing nivolumab courses. The patient died of hypopharyngeal cancer progression.

Background Granulosa cell tumor (GCT) is a type of ovarian sex cord-stromal tumor with low-grade malignancy, which can recur long after primary resection. All reports on GCTs in the liver describe cases of metastases, while there are no previous reports of primary GCTs originating from the liver. We report a case of GCT, with recurrence of liver metastasis long after ovariectomy, which was subsequently resected by a right trisectionectomy. Case presentation A 76-year-old woman presented with a history of surgical resection of an ovarian tumor performed 30 years previously; no details of the tumor were available. When she was 68 years old, an abdominal ultrasound revealed a small liver mass, which was diagnosed as a hepatic hemangioma with slow growth. Outpatient follow-up was discontinued for 5 years, and the patient was not examined again until the age of 76 years. At this point, the tumor had substantially increased in size, and surgical resection was required owing to suspicion of malignancy. The patient was then referred to our hospital. Contrast-enhanced computed tomography (CT) showed a large tumor, approximately 18 cm in size, occupying the right lobe and medial section of the liver. After percutaneous transhepatic portal vein embolization, a right trisectionectomy was performed. The histopathological findings of the resected specimen showed that the tumor cells had “coffee bean-like” nuclear grooves, which are characteristic of a GCT. Acidophilic non-structural Call-Exner bodies were also observed. Inhibin-α, CD99, and CD56 markers of sex cord-stromal tumors were detected on immunohistological examination; all pathology suggested a GCT. We considered the tumor to be a liver metastasis of a previous ovarian GCT that was resected 30 years prior by ovariectomy. There was no recurrence for > 15 months after the hepatectomy. Conclusions We report a case of a GCT in the liver, which was identified to be a liver metastasis. Right trisectionectomy was subsequently performed for tumor resection. Clinicians should be aware that ovarian GCTs may recur in the liver, and that GCT recurrence may occur long after ovariectomy of the primary ovarian GCT.

Various approaches to hepatectomy have been proposed for cT2 gallbladder cancers (GBC), but the optimal management strategy remains unclear. The aim of this study is to assess the effectiveness of using an indocyanine green (ICG)-based intraoperative navigation system during hepatic resection for cT2 GBC. From September 2007 to December 2017, 24 consecutive patients diagnosed with cT2 GBC underwent hepatic resection using ICG navigation. After cannulation of the cholecystic artery, ICG diluted with dissolution liquid was injected and ICG fluorescence illumination was visualized with the HyperEye Medical System. And additional histopathological examination was performed on the most recent 15 of the 24 patients for detection of microscopic liver metastasis. For all patients, the disease-free survival rate was 59.1% at 5 years and overall survival rate was 86.2% at 5 years. Microscopic liver metastasis was detected in the resected liver in 3 (20%) of 15 patients, whose site of liver was S6, S5, and S5, respectively. The weight of the liver resected using ICG navigation was significantly smaller than that of S4a/S5 segmentectomy (P

Glomus tumors originate from a neuroarterial structure called the glomus body, and grow mostly in soft tissue. It is rare for glomus tumors to develop in the respiratory system. The patient of the present case had an abnormal shadow in the right lung on chest X-ray, and computed tomography (CT) findings displayed a lung tumor in the right S6. Bronchoscopy was performed for the diagnosis of the lung tumor, and a polypoid bronchial tumor was unexpectedly found to occupy the right B3. The bronchial tumor was diagnosed as a glomus tumor, and the lung tumor was diagnosed as an adenocarcinoma. The bronchial glomus tumor was cauterized by argon plasma coagulation (APC). Three weeks after the cauterization by APC, the right lower lobectomy was performed for the treatment of the lung adenocarcinoma. The patient has remained disease free for 2 years.

We investigated the quantification of Ki-67 staining using digital image analysis (IA) as a complementary prognostic factor to the modified National Institutes of Health (NIH) classification in patients with gastrointestinal stromal tumor (GIST). We examined 92 patients, focusing on the correlation between age, sex, primary tumor site, tumor size, predominant histologic type, mitotic index, modified NIH classification (low/intermediate vs high), Ki-67 quantitation, and recurrence-free survival (RFS). We compared two IA processes for whole slide imaging (WSI) and manually captured image (MCI) methods. A Ki-67 quantitation cutoff was determined by receiver operator characteristics curve analysis. In the survival analysis, the high-risk group of a modified NIH classification, a mitotic count >5 per 20 high-powered fields, and Ki-67 cutoffs of ≥6% and ≥8% obtained by IA of the WSI and MCI methods, respectively, had an adverse impact on RFS. On multivariate analysis, each Ki-67 quantitation method strongly predicted prognosis, more strongly than the modified NIH classification. In addition, Ki-67 quantitation using IA of the MCI method could stratify low or intermediate risk and high risk GIST patients. Thus, IA is an excellent tool for quantifying Ki-67 to predict the prognosis of GIST patients, and this semiautomated approach may be preferable for patient care.

Isolated congenital pulmonary valvular stenosis is a relatively common abnormality. A 52-year-old woman with an asymptomatic cardiac murmur since her childhood visited our hospital. The peak pressure gradient across the pulmonary valve (PV) was calculated 25 mmHg by Doppler velocity during the transthoracic echocardiography, the severity was graded into mild. The cardiac computed tomography indicated a dome-shaped PV with an equilateral triangle orifice without commissural fusion. No case has been described in a triangle orifice, it will be necessary to follow up carefully.

Introduction: Meningioma is mostly a benign tumor, but sometimes it is malignant, and there have been reports of distant metastases. Patient concerns: The patient, a woman in her 40s, was under follow-up after resection of an ectopic malignant meningioma originating in the left axilla. She was referred to our department because of a nodule shadow in the right lung on chest computed tomography (CT) 3 years and 5 months postoperatively. Diagnosis: Chest CT showed a 1.0 cm nodule shadow in the right S4, which was positive on positron emission tomography-CT; no abnormality was found in any other organ. Therefore, it was considered to be a metastatic lung tumor. Interventions: Right middle lobe partial resection was performed using thoracoscopic surgery, and a diagnosis of pulmonary metastasis of ectopic malignant meningioma was made by histopathology and immunohistochemistry. Outcomes: In this case, complete resection was possible. Conclusion: Meningioma occurs mainly in the cranium, and occurrence in the soft tissue of the extremities is extremely rare. To our knowledge, ours is the first report of a histologically malignant ectopic meningioma with metastasis to the thoracic cavity.

Background Pancreatic vascular malformation causes epigastric pain, pancreatitis, portal vein hypertension, bleeding, and rupture. It is a rare disease, with most pancreatic vascular malformations being arteriovenous malformations (AVMs) and the other types of malformations being rare. We report a case of capillary lymphatic malformation (CLM) in the pancreatic uncinate process. Case presentation A 74-year-old woman, who presented with complaints of repeated upper abdominal pain, was admitted to our institution. Contrast-enhanced dynamic computed tomography (CT) scan revealed that the tumor in the pancreatic uncinate process had a poor contrast effect in the arterial phase and a small contrast effect in the equilibrium phase, which are suggestive of a benign disease-like vascular malformation. However, we suspected that it could possibly be a malignant tumor because the tumor size tended to increase over time; thus, we decided to perform a surgery. We resected the tumor through a partial resection of the pancreas. Macroscopically, the cut surface of the tumor had a spongioid appearance. Histopathological examination findings showed a mixed shape of small capillaries and lymphatic ducts. The patient was diagnosed with CLM according to the International Society for the Study of Vascular Anomalies (ISSVA) classification, based on the histological appearance and immunostaining findings. The postoperative course of the patient was uneventful. Conclusions We reported a case of pancreatic vascular malformation, specifically a CLM, which was completely resected through a partial pancreatectomy.

Hypertrophic pachymeningitis (HP) is a rare disorder characterized by diffuse thickening of the dura mater with resultant neurologic deficits. HP develops secondary to various conditions or idiopathically usually in adults but rarely in children. We describe a 3-year-old female child with idiopathic HP. Her HP involved the entire central nervous system with progression into the brainstem. The lesion responded poorly to pulsed steroids or any immunosuppressants. The brainstem lesion grew rapidly and formed various nodules that ultimately resulted in brain death. This is the first fatal case of HP in a child.

Survivin is expressed in the nucleus and/or cytoplasm of various malignant cells. Nuclear survivin is critical for the completion of mitosis, while cytoplasmic survivin functions as an inhibitor of apoptosis. The expression of survivin has been reported to be associated with the aggressiveness of certain types of cancer. The present study examined the association between cigarette smoking history and the expression of survivin and Ki-67 in lung adenocarcinomas of pathological (p) stages I, II and III. The expression of survivin and Ki-67 in adenocarcinomas was also compared with that of other p-stage I lung cancers, including squamous cell carcinoma (SqCC), large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SmCCs), of patients with a smoking history. In adenocarcinomas at p-stage I, labeling indices (LIs) of nuclear survivin and Ki-67 were significantly higher in tissue samples from smokers than those from non-smokers; however, the nuclear survivin and Ki-67 LIs in p-stage II and III adenocarcinomas from non-smokers and smokers were similar to those in p-stage I adenocarcinomas of smokers. The nuclear survivin and Ki-67 LIs in adenocarcinomas of smokers at p-stage I were lower than those in SqCCs, LCNECs and SmCCs of smokers at the same stage. Smokers with adenocarcinoma also exhibited a higher survival rate compared with that of smokers with SqCCs, LCNECs and SmCCs. The present results indicated that a history of smoking is associated with increased nuclear survivin and Ki-67 expression in lung adenocarcinomas of p-stage I, but not p-stages II or III. In addition it was revealed that, in smokers, the nuclear survivin and Ki-67 expression in p-stage I adenocarcinomas was lower than that of other p-stage I lung cancer types, and was associated with an enhanced survival rate. In conclusion, smoking is associated with the histogenesis of lung adenocarcinoma but not with the development of lung adenocarcinoma, based on the nuclear expression levels of Ki-67 and survivin.