[A Case of Colon Cancer with Peritoneal Dissemination and Liver Metastasis That Responded to Comprehensive Treatment by Perioperative Chemotherapy and Cytoreductive Surgery].

A 64-year-old man was referred to our hospital to determine the cause of fecal occult blood. Colonoscopy revealed a type Ⅱtumor located in the ascending colon. Histopathologic analysis of the tumor biopsy specimen revealed moderately differen- tiated, tubular adenocarcinoma with KRAS exon 2(G12V)mutation. FDG-PET/CT revealed high trace accumulation in the S4 of the liver and in multiple sites spread across the abdominal cavity(cT4aN1M1c2[H1, P3], cStage Ⅳc). Chemotherapy using S-1 plus oxaliplatin(SOX)with bevacizumab(Bmab)was administered. After 8 courses of SOX with Bmab, the volume of the ascending colon cancer and liver metastasis reduced, and peritoneal disseminations disappeared. We, therefore, considered that curability B resection was suitable, and performed right hemicolectomy, total omentectomy, and resection of the rectovesical peritoneum. Histopathological examination of surgical specimens revealed extensive fibrosis from the submucosa to subserosal tissue with some tubular adenocarcinoma cells(histological effect: Grade 2). For maintenance therapy, trifluri- dine/tipiracil plus Bmab was administered after cytoreduction. The patient is in remission for 26 months without recurrence. Perioperative chemotherapy and cytoreductive surgery are useful for the treatment of colon cancer with diffuse peritoneal dissemination.

[A Case of Metastatic Colorectal Cancer Refractory to Standard Chemotherapies Treated with TAS-102 with Bevacizumab].

A 51-year-oldwoman with lung, liver, andd istant lymph node metastases from sigmoidcolon cancer was treatedusing TAS-102 with bevacizumab as fourth-line chemotherapy. There was a 35%decrease in the size of target lesions after the first 4 cycles of therapy, and disease control has been maintained for 9 months. The only Grade 3 or worse adverse event experiencedwas neutropenia. In patients with refractory colorectal cancer, the combination of TAS-102 with bevacizumab might be an effective andsafe treatment.

[A Case of Multiple Pancreatic Metastases from Renal Cell Carcinoma Diagnosed Using EUS-FNA].

The patient was a 79-year-old man, who underwent left nephrectomy for left renal cell carcinoma in 2007. In March 2015, he complained ofthirst, polydipsia, and polyuria. A slight elevation ofamylase levels was detected following laboratory testing. Abdominal CT revealed well-enhanced tumors in the pancreatic head and tail. MPD was dilated in the pancreatic body and tail. Endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)was used to obtain additional pathological findings. We diagnosed multiple pancreatic metastases from renal cell carcinoma using cell block sections from EUS-FNA ofthe pancreatic head tumor. We also identified worsening of diabetes control due to pancreatic disease. A subtotal stomachsparing pancreaticoduodenectomy and a distal pancreatectomy were performed in June 2015. Histological examination confirmed clear cell carcinoma metastases from RCC in both tumors. The patient remains alive without recurrence approximately 1 year after surgery. Glycemic control has improved with a decrease in insulin levels. Cell block sections from EUS-FNA are useful in the diagnosis of pancreatic disease. Although postoperative follow-up ofthe remnant pancreas is important, preservation ofthe pancreas should be considered for multiple pancreatic metastases when complete tumor removal is possible.

[Analysis of Pancreaticoduodenectomy for Elderly Patients Aged 75 Years or Older].

The feasibility of pancreaticoduodenectomy (PD) for elderly patients is controversial. Of 51 patients with pancreatic or bile duct tumor who underwent PD (except portal vein resection), the surgical results of 27 elderly patients aged 75 years or older (elderly group) we retrospectively evaluated and compared with those of 24 patients younger than 75 years (younger group). Although ASA-PS was significantly higher in the elderly group, we did not observe any significant difference in other background characteristics, complications, or length of hospital stay between the two groups. This study suggests that PD is probably safe and feasible with the appropriate surgical indication for elderly patients.

[A Case of Extrahepatic Hepatocellular Cancer Discovered during Gynecological Laparoscopic Surgery].

Recently, laparoscopic surgery has become increasingly popular because of its lesser invasiveness, including smaller incisions, and fewer post-operative complications. It is also possible to observe the abdominal cavity by laparoscopy. We report a hepatocellular carcinoma arising in an accessory liver lobe detected during gynecological laparoscopic surgery. A 48-year-old woman who was undergoing laparoscopic hysterectomy for uterine fibroids was found to have a protruding, extrahepatic pedunculated tumor by intraoperative observation of the abdominal cavity during the fibroid procedure. We suspected FNH based on preoperative imaging findings, including abdominal ultrasound, computed tomographic scanning, and magnetic resonance imaging. We performed a laparoscopic partial hepatectomy. The cut surface of the tumor was similar to normal liver tissue. The pathological findings identified normal liver tissue and vessels, suggesting it was the accessory liver lobe. It also included a well-differentiated hepatocellular carcinoma. The final diagnosis was hepatocellular carcinoma arising in the accessory liver lobe. There have been no prior reports of extrahepatic liver tissue detected during gynecological surgery. This case reminded us of the importance of intra-abdominal observation during laparoscopic procedures. The opportunities to discover other cases of extrahepatic liver tissue by laparoscopy will increase.

[A Resected Case of Acinar Cell Carcinoma Diagnosed by Endoscopic Ultrasound Guided Fine-Needle Aspiration Prior to Surgical Treatment].

Acinar cell carcinoma (ACC) of the pancreas is an extremely rare tumor type, accounting for approximately 1% of all pancreatic neoplasm. Here, we report a rare case of ACC of the pancreas diagnosed on the basis of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) findings prior to surgical treatment. A 73-years-old woman was being followed-up for chronic hepatitis C at our institution. Abdominal enhanced computed tomography showed an enhanced region, 16 mm in size, near the head of the pancreas on early-phase images. Magnetic resonance cholangiopancreatography did not show interruption or dilatation of the main pancreatic duct. Fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed an increased FDG uptake in the mass (SUVmax=12.7). EUS-FNA indicated a diagnosis of ACC, and pancreaticoduodenectomy was performed. Pathological examination confirmed the diagnosis of ACC. The patient was discharged after an 18-day hospital stay. Two years later, the patient has not shown any sings of recurrence.

[Analysis of portal vein resection during pancreaticoduodenectomy in patients with pancreatic cancer].

The feasibility of portal vein resection (PVR) during pancreaticoduodenectomy (PD) for cancer of the pancreatic head is controversial. We retrospectively evaluate the surgical results and prognosis of 26 patients with pancreatic cancer who received PD with PVR (PVR group, n=14) or without PVR (non-PVR group, n=12). The operation time was significantly greater in the PVR group, with a mean time of 13.6 ± 2.4 minutes. There were no differences between the PVR and non-PVR groups in the incidence of complications or the number of days in hospital. In the PVR group, 7 patients were histopathologically diagnosed with portal vein invasion (PV), but there was no difference in the postoperative survival between PV negative and positive patients. PVR during PD appears to be a safe and feasible treatment for appropriate stage pancreatic cancer patients receiving adjuvant chemotherapy.

[A case of long-term survival in rectal cancer with late lung and kidney metastases treated with combined multimodality therapy].

A 59-year-old man was diagnosed with rectal cancer and a low anterior resection was performed. Bilateral lung metastases appeared 4 years and 4 months after the primary surgery. The lung metastases were resected and FOLFOX6 neoadjuvant chemotherapy was administered. An abdominal computed tomography (CT) scan 7 years and 11 months after the primary surgery revealed bilateral multiple lung metastases, a left renal tumor, and swelling in the surrounding lymph node. A left nephrectomy and lymph node dissection were performed. A diagnosis of renal tumor from rectal cancer metastasis was made. For the lung metastases, chemotherapy (sLV/5FU2+Bmab) was administered in 26 courses and stable disease was achieved. It is important to combine adequate surgical resection and systemic chemotherapy for long survival.

[A case of partial hepatectomy and gastrectomy for hepatocellular carcinoma with direct invasion to the stomach].

An 81-year-old man treated with chronic hepatitis C virus (HCV)-related hepatitis and hepatocellular carcinoma (HCC) was diagnosed in 2010 with HCC recurrence (subclass S2) on computed tomography (CT). He refused surgery and was followed up without treatment. In 2012, he was admitted to our hospital because of hematemesis. Gastrointestinal endoscopy revealed a large tumor in the upper gastric corpus, and pathological examination of the tumor revealed HCC; hence, we diagnosed the patient with direct HCC invasion to the stomach. Although active bleeding from the tumor was controlled, he experienced repeated episodes of hematemesis, and the tumor increased in size. Therefore, partial hepatectomy and gastrectomy were performed. It was confirmed that the tumor invaded the stomach wall. Although surgery was effective for gastrointestinal bleeding caused by HCC invasion, the patient died 12 months after surgery because of multiple liver metastases and exacerbated liver failure.

Intratumoral regulatory T cells as an independent predictive factor for pathological complete response to neoadjuvant paclitaxel followed by 5-FU/epirubicin/cyclophosphamide in breast cancer patients.

Anti-tumor immunity is thought to play a significant role in chemotherapeutic response of breast tumors. In the present study, we investigated whether tumor infiltrating FOXP3+ regulatory T cells, CD8+ cytotoxic T cells, and IL17F+ helper T cells were associated with a pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Breast cancer patients (stages II and III, n = 180) who were treated with NAC consisting of sequential weekly paclitaxel followed by 5-FU/epirubicin/cyclophosphamide were included for this study. Core needle tumor specimens obtained before NAC were immunohistochemically examined for FOXP3, CD8, and IL17F. Intratumoral infiltration of FOXP3+, CD8+, and IL17F+ T cells was observed in 62.2, 80.0, and 62.2 % of tumors, respectively. FOXP3 and CD8 infiltrates, but not IL17F infiltrate, were significantly (P < 0.001 and P = 0.007, respectively) associated with a high-pCR rate (31.3 and 25.7 %, respectively), and breast tumors with both FOXP3 and CD8 infiltrates showed the highest pCR rate (33.0 %). Multivariate analysis indicated that only FOXP3 infiltrates (P = 0.014) and the conventional predictive factor Ki67 (P = 0.031) were statistically significant and independent predictors of pCR. Breast tumors with FOXP3 and CD8 infiltrates were more likely to achieve pCR. FOXP3 infiltrate, in combination with Ki67, could thus be used as a clinically useful predictor of response to NAC. The possible indirect mechanism through which chemotherapy exerts its anti-tumor activity, i.e., enhancing anti-tumor immunity by inhibiting FOXP3, was also suggested.

De-escalated neoadjuvant therapy with nanoparticle albumin-bound paclitaxel and trastuzumab for low-risk pure HER2 breast cancer.

PURPOSE: Neoadjuvant trastuzumab combined with anthracycline and taxane is now considered a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A less toxic, non-anthracycline regimen has been considered as a treatment option for patients with node-negative small tumors. Estrogen receptor-negative and HER2-positive (pure HER2) tumors are more likely to achieve a pathological complete response (pCR). This study evaluates the activity and safety of neoadjuvant nanoparticle albumin-bound paclitaxel (nab-PTX) plus trastuzumab for pure HER2 breast cancer in patients with low risk of relapse. METHODS: We treated patients with tumors measuring ≤ 3 cm, node-negative, pure HER2 breast cancer using neoadjuvant nab-PTX 260 mg/m2 with trastuzumab every 3 weeks for four cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery conversion rate, safety, and disease-free survival. Depending on the pathological findings of surgical specimens, the administration of adjuvant anthracycline could be omitted. RESULTS: Eighteen patients were enrolled. No patient required dose delays or reductions; none showed disease progression, and all patients underwent surgery as scheduled. Of the 18 patients, 66.7% achieved pCR, and the adjuvant anthracycline regimen was omitted for all patients. The incidence of severe adverse events was quite low. CONCLUSION: This less toxic, anthracycline-free regimen appears to be a significantly effective neoadjuvant therapy for patients with pure HER2 breast cancer at low relapse risk.

Non-small-cell lung cancer associated with non-thymomatous myasthenia gravis.

A non-small-cell lung cancer without distant metastases was incidentally found in a 77-year-old man who had suffered from myasthenia gravis (MG) without thymoma. The patient's condition was stabilized by oral pyridostigmine bromide which he had taken during the past 6 years. He simultaneously underwent thymectomy and left lower lobectomy with regional lymph node dissection. Although postoperative myasthenic crisis occurred, mechanical ventilation and intravenous steroid pulse relieved the patient and the symptoms improved thereafter. Cases of operable lung cancer with non-thymomatous MG have rarely been reported and the appropriate therapeutic strategy for such cases remains to be debated. Their causal association remains to be identified, whereas some studies have implied that immune disorder due to the abnormal thymus might possibly enhance the oncogenesis of extrathymic malignancies. Myasthenic crisis should also be taken into account in postoperative management of MG patients who simultaneously undergo thymectomy and lobectomy for synchronous lung cancer.

Pulmonary lymphoma of mucosa-associated lymphoid tissue type followed as a long-standing indeterminate lesion in immunoglobulin M-type paraproteinemia.

An 82-year-old woman with monoclonal immunoglobulin (Ig) M-type paraproteinemia had a large opacity in the right lung field. The abnormal shadow on roentgenogram had persisted for more than 6 years since the initial diagnosis of paraproteinemia, which had been diagnosed as Waldenström's macroglobulinemia (WM). Computed tomography revealed the lesion as a pulmonary tumor which was finally diagnosed as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) after surgical removal. MALT lymphoma constitutes the majority of primary pulmonary lymphomas and is often associated with monoclonal IgM-type paraproteinemia as well as WM, a distinctive lymphoproliferative disorder. Pulmonary MALT lymphoma should frequently be suspected in case of an indeterminate pulmonary tumor with IgM-type paraproteinemia.

Methylated DNA and high total DNA levels in the serum of patients with breast cancer following neoadjuvant chemotherapy are predictive of a poor prognosis.

In a previous study, we established a one-step methylation-specific polymerase chain reaction (OS-MSP) assay for the detection of methylated DNA (met-DNA) and total DNA levels in serum. For the present study, this OS-MSP assay was used for patients with breast cancer treated with neoadjuvant chemotherapy (NAC) in order to investigate the prognostic significance of met-DNA and total DNA levels. Following treatment with NAC and prior to surgery, serum samples obtained from 120 patients with stage II/III breast cancer were subjected to the OS-MSP assay for analysis of the glutathione S-transferase pi 1, Ras association (RalGDS/AF-6) domain family member 1 and retinoic acid receptor ß2 genes. The detection of methylation in a minimum of one of these genes indicated a positive outcome of the assay. The total DNA content of the serum was also determined. Of the 120 stage II/III patients, seven (6%) were positive for met-DNA in serum and showed a significantly worse overall survival (OS) time compared with patients negative for met-DNA (n=113) (5-year OS, 43 vs. 85%; P=0.002). The patients with high total DNA levels in serum (n=40) also showed a significantly worse OS compared with those with low total DNA levels (n=80) (65 vs. 91%; P<0.001). The presence of met-DNA and high total DNA levels in the serum were found to be significant prognostic factors that are independent of a pathological complete response by multivariate analysis. Following NAC, met-DNA and high total DNA levels in the serum detected with the OS-MSP assay constitute novel prognostic factors for patients with breast cancer; this may be clinically useful for the prognosis prediction for patients who do not achieve a pathological complete response following NAC.