Multicenter Prospective Cohort Study of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer (YPB-001).

OBJECTIVES: The present multicenter prospective observational study investigated the effectiveness and safety of neoadjuvant chemotherapy (NAC) for patients with borderline resectable pancreatic cancer (BRPC) and those with RPC contacting major vessels, with respect to a historical control of upfront surgery. MATERIALS AND METHODS: Patients with BRPC and RPC contacting major vessels were prospectively registered and administered NAC with durations and regimens determined by the corresponding treating physician. Our primary aim was to assess the R0 resection rate, and secondary aim was to evaluate safety, resection rate, time to treatment failure, overall survival, and response rate. RESULTS: Fifty of 52 enrolled patients were analyzed; 2 with serious comorbidities died during treatment. Thirty-one patients underwent resection, with R0 resection being achieved in 26 (52% of total and 84% of all resected cases). Univariate and multivariate analyses indicated age (≥75 years) as the only independent predictor of nonresection. Median progression-free survival and median survival time were longer in the prospective cohort than in the historical cohort. CONCLUSIONS: Overall, NAC for BRPC in real-world setting might yield R0 resection rates similar to those reported in previous clinical studies. Development of safe regimens and management strategies that can maintain treatment intensity in geriatric patients is warranted.

[A Case of Advanced Gastric Cancer Who Experienced Multiple Immune-Related Adverse Events with Nivolumab and SOX Therapy].

A 59-year-old woman who has HER2-negative advanced gastric cancer with peritoneal dissemination was treated with nivolumab plus SOX therapy as primary treatment, and hemorrhagic cystitis occurred on the 28th day after the 6 courses. On the 21st day after the 7 courses, right knee arthralgia appeared, and on the 26th day, she was admitted to the hospital due to a fever of 39℃ and anorexia. After admission, frequent diarrhea occurred and new symptoms of neck pain and left knee arthralgia appeared. Abdominal CT showed increased fatty tissue density around the sigmoid colon, and wall thickening and contrast enhancement of the mucosal surface of the bladder. Lower gastrointestinal endoscopy revealed the diffuse redness and erosions in some areas, and lymphocytic infiltration in the epithelium of the crypts was seen in biopsy from the erosions. The hemorrhagic cystitis was aseptic pyuria. Therefore, we suspected that the series of symptoms were immune-related adverse events(irAE)and started prednisolone 50 mg(1 mg/kg/day), which quickly relieved the diarrhea, cystitis and arthralgia. As a result, the patient was diagnosed as having irAE. We report a case of advanced gastric cancer who experienced multiple irAE with nivolumab plus SOX therapy, with some discussion of the literature.

[A Case of Simultaneous Laparoscopic Surgery for Intrahepatic Cholangiocarcinoma and Sigmoid Colon Cancer].

The patient was an 83-year-old woman. CT scan showed a 20 mm mass in the surgical anatomy of the medial segment (S4)of the liver, but the patient refused to undergo surgery and continued periodic clinical follow-up. After 1 year and 3 months of initial examination, a CT scan showed an enlargement of 36 mm. Therefore, surgical treatment was adopted. Preoperative lower gastrointestinal endoscopy revealed a type 1 tumor of the sigmoid colon quarter circumference 30 mm from the anal verge, and the biopsy led to a diagnosis of adenocarcinoma equivalent to tub 1. The hepatic mass showed heterogeneous contrast effect centered on the arterial phase margins and prolonged contrast effect in the equilibrium phase. Since the liver tumor was a single S4 mass with a 36 mm diameter, laparoscopic sigmoidectomy and laparoscopic partial hepatic resection were performed subsequently. Pathology results showed that the sigmoid colon tumor and hepatic S4 mass were predominantly well-differentiated and moderately-differentiated adenocarcinomas, respectively. Immunohistochemical results were cytokeratin 7 antibody-positive and cytokeratin 20 antibody-negative, leading to a definitive diagnosis of intrahepatic cholangiocarcinoma. The patient's postoperative course was well and was discharged from the hospital on postoperative day 12. After 1 year postoperatively, the patient remains recurrence-free.

[A Case of Tumor Embolization to the Internal Iliac Vein Four Years after the Surgery for Rectal Cancer].

60-year-old man was admitted to our hospital with a chief complaint of melena. Lower gastrointestinal endoscopy revealed a type 2 tumor on the anterior wall of the rectum(Rb). He was referred to our department, and he underwent abdominoperineal rectal resection with D3 dissection and right lateral node dissection for Rb, cT2, N0, M0 intestinal cancer. Pathological diagnosis was a tub2, pT2, N0, Ly0, V0, pDM0(30 mm), pPM0(160 mm), pR0, pStage Ⅰ cancer. Therefore, postoperative adjuvant chemotherapy was not performed. Subsequent follow-up examinations were conducted on a regular basis to confirm no recurrence. However, 4 years after the surgery, high levels of tumor markers, such as CEA(59.2 ng/mL) and CA19-9(75.5 U/mL), were detected. CT showed tumor embolism to the internal iliac vein and multiple lung metastases. After IVC filter placement, chemoradiotherapy was performed. Although the tumor embolism disappeared, multiple lung metastases increased. Additionally, brain metastasis appeared 6 years after the operation. After that, according to the policy of BSC, he died 7 years after the surgery.

[A Case of Laparoscopic Gastric Local Resection for Simultaneous Multiple Gastric GIST Discovered Owing to Gastrointestinal Bleeding].

An 80-year-old woman with anemia presented to our hospital. Upper gastrointestinal endoscopy revealed a 4 cm submucosal tumor(SMT)with a delle and 2 cm SMT in the upper part of the stomach. CT revealed sustained enhancement of both tumors. The posterior tumor was an intraductal growth, and the anterior tumor was an extravascular growth. We performed a laparoscopic gastric local excision for the multiple SMTs. The anterior tumor was resected with an automatic suture instrument. However, the posterior tumor could not be identified from within the abdominal cavity because it was resected while confirming using an endoscope, and all layers were sutured. On histopathological examination, the posterior tumor was 40mm in size, with spindle-shaped atypical cells growing in the submucosal layer. Immunostaining was c-kit(+), CD34(+), S-100(-), and desmin(-). The Ki-67 level was<1%. The anterior wall tumors showed similar findings, but some showed smooth muscle differentiation. From the results, a diagnosis of simultaneous multiple gastric GIST(low risk)was made.

[A Case of Metastasis of Ascending Colon Cancer to the Small Intestine That Was Diagnosed Based on Ileus].

A 69-year-old man was administered an ileus tube for ileus by ascending colon cancer. The next day, he underwent right hemicolectomy with D3 lymph node dissection for perforative peritonitis due to ascending colon cancer. The pathological diagnosis was A, type 2, muc>tub1, pT3, pN0. M0, pStageⅡ. He received 5 courses of UFT/Leucovorin(LV)chemotherapy. Two years later, he was hospitalized for ileus. He underwent surgery. The peritoneal dissemination was absent in the surgical findings. We resected a small intestinal tumor from the oral side of anastomosis. Because the tumor appearance and pathological findings were similar to those of ascending colon cancer, the patient was diagnosed with metastasis of ascending colon cancer to the small intestine. We report our rare encounter with metastases of colorectal cancer to the small intestine.

[A Case of Rectal Neuroendocrine Carcinoma That Showed a Sharp Turning Point after Neoadjuvant Radiochemotherapy and Conversion Surgery].

A 45-year-old man presented with the chief complaint of anal discomfort to a previous doctor. The symptoms remained after undergoing seton surgery following the diagnosis of intermuscular anal fistula. CT showed a tumor that was 3 cm in diameter on the right wall of the rectum, and he received a diagnosis of neuroendocrine carcinoma(NEC)based on a biopsy. Subsequently, he was admitted to our hospital. Liver metastasis accompanied NEC, and chemotherapy was performed for stage Ⅳ diagnosis. We detected tumor disappearance after administering 8 courses of CDDP plus CPT-11. However, after 3 months, a 1 cm nodule appeared at the primary lesion, which was considered as recurrence. We selected reintroduction of CDDP plus CPT-11 treatment, but the tumor progressed. CDDP plus VP-16 plus radiation therapy was introduced, and tumor shrinkage was observed without distant metastasis. We judged that radical resection was possible, and performed Miles' operation, total prostate gland resection, and urethra reconstruction. He was discharged on the 28th day after surgery. The pathological findings indicated neuroendocrine small cell carcinoma, and the CRT effect was judged as Grade 2 and curability A. However, he was admitted to the emergency room following convulsions on the 46th day after surgery was performed. CT revealed multiple cerebral metastasis, meningeal dissemination, and liver metastasis. He underwent cyber knife surgery for brain metastasis. Drainage was required for cerebral hypertension due to meningeal dissemination. He died on the 115th postoperative day.

[Effect of Pegfilgrastim Primary Prophylactic Administration on Relative Dose Intensity(RDI)in Postoperative Adjuvant Chemotherapy(TC Therapy)for Breast Cancer - A Single-Center, Retrospective Study].

This study assessed the effect of pegfilgrastim in patients with early stage breast cancer who were receiving docetaxel and cyclophosphamide(TC)therapy(75mg/m / 2 docetaxel plus 600 mg/m2 cyclophosphamide). In total, 17 patients who were to receive 4 planned cycles of TC therapy every 3 weeks were included in this study. Of the 17 patients, 10 who received pegfilgrastim after January 2016 formed the Peg-G group and 7 who did not receive pegfilgrastim until December 2015 formed the control group. We observed a high successful execution rate and relative dose intensity(RDI)with docetaxel in both groups. The successful execution rates were 100% in the Peg-G group and 42.8% in the control group. The RDI was 86.5%(65.4-100%)in the Peg-G group and 52.5%(48.0-58.0%)in the control group. This study showed that the use of pegfilgrastim results in a high successful execution rate and RDI in patients with early stage breast cancer undergoing TC therapy.

[Ten-year survival of a patient with advanced gastric cancer with no. 16 lymph node metastases after total gastrectomy and paraaortic lymphadenectomy].

When no other non-curative treatment options are available, R0 resection can be achieved with paraaortic lymphadenectomy for patients with advanced gastric cancer with No.16 lymph node metastases. Herein, we report of a patient who underwent R0 resection for gastric cancer with No.16 lymph node metastases and who achieved long-term survival.

Clinical impact of tumor invasion depth staging of esophageal squamous cell carcinoma using endoscopic ultrasonography.

BACKGROUND/AIMS: To demonstrate how EUS tumor staging has a practical effect on deciding the treatment strategy for esophageal carcinoma, we retrospectively evaluated the clinical impact of thin-probe EUS staging. METHODOLOGY: The results of EUS performed 54 times were classified according to clinical impact into three grades (none, supportive, and important) and analyzed to assess their impact on the treatment strategy on individual occasions. RESULTS: EUS was important in determining treatment strategy for 23 of 39 lesions (59.0%) in the EUS-superficial group and supportive for 16 lesions (41.0%). The clinical impact of EUS for 15 lesions in the EUS-deep group was graded important for 8 lesions (53.3%), supportive for 6 lesions (40.0%) and none for one lesion (6.7%). CONCLUSIONS: Thin-probe EUS is expected to have some clinical impact on the determination of treatment strategies for squamous cell carcinoma of the esophagus.

[A case of long-term survival of recurrent gastric cancer successfully treated with multidisciplinary therapy].

A 73-year-old male patient underwent total gastrectomy for advanced gastric cancer in December 2000. The final diagnosis was 1 MU, ant, type 3, 67x47 mm, pT2 (ss), pN1 (#1, 3, 4d), sP0, sH0, CY0, cM0, fStage II, tub 2, int, inf beta, ly3, v3, 2 L, post, type 2, 42x40 mm, pT2 (mp), pN1 (#1, 3, 4d), sP0, sH0, CY0, cM0, fStage II. Although we began adjuvant chemotherapy with UFT 300 mg/day, a solitary liver metastasis in the S6 sub-segment of the liver was diagnosed 15 months after the first operation. He received RFA for liver metastasis, and the protocol was changed to S-1. Two-time recurrence of S6 was controlled by RFA but liver metastasis recurred again. So we performed posterior segmentectomy of the liver 30 months after the first operation. CT showed a solitary paraaortic lymph node metastasis 60 months after the first operation (24 months after hepatectomy). He showed a stable disease for 1 year, so he was given radiation of paraaortic lymph node metastasis at a total dose of 36 Gy (4.5 Gyx8 times) after 72 months from the first operation. One hundred two months passed from first operation. The patient remains alive without any recurrence, and this multidisciplinary therapy proved to be effective.

[A case of advanced gastric cancer with histological complete response after S-1 chemotherapy].

A 58-year-old man of unresectable gastric cancer was treated with S-1 (120 mg/body/day) after gastrojejunostomy. After 5 courses of orally administration of S-1 for 4 weeks and withdrawal for 2 weeks, partial response (PR) was obtained clinically and distal gastrectomy was performed. The histological diagnosis showed no residue of carcinoma with both HE and immunohistochemical staining. The patient has been in good health and no recurrence has occurred for about 4 years and 4 months after resection.

Adoptive immunotherapy for pancreatic cancer: cytotoxic T lymphocytes stimulated by the MUC1-expressing human pancreatic cancer cell line YPK-1.

MUC1 is a tumor-associated antigen that is overexpressed in invasive ductal carcinomas of the pancreas (PC). MUC1-specific cytotoxic T lymphocytes (CTLs) recognize MUC1 molecules in a HLA-unrestricted manner. In this study, we performed adoptive immunotherapy (AIT) in patients with PC with CTLs stimulated by the MUC1-expressing human PC cell line YPK-1. To induce CTLs, peripheral blood mononuclear cells (PBMCs) were cultured for 3 days with inactivated YPK-1 cells and then stimulated with interleukin (IL)-2 for 7 days. The cytotoxicity of these cells against human cancer cell lines was analyzed, and a variety of antibodies were evaluated for their ability to inhibit cytotoxicity. We treated 8 patients with unresectable PC and 20 patients with resectable PC postsurgically. CTLs were induced as described above, suspended in 100 ml saline and injected intravenously. Induced CTLs were cytotoxic against 5 MUC1-expressing PC cell lines and a breast cancer cell line, regardless of the HLA phenotype. Low cytotoxicity was observed in 7 MUC1-negative cancer cell lines. Anti-CD3 monoclonal antibody (mAb) or anti-CD8 mAb strongly inhibited cytotoxicity against YPK-1, whereas anti-class I mAb showed no inhibition. YPK-1 cells incubated with anti-MUC1 mAb also showed low cytotoxicity. Clinically, the median survival time was 5.0 months for patients with unresectable PC treated with AIT. None of the 5 patients without liver metastasis showed hepatic recurrence. The median survival time was 17.8 months for 18 out of 20 patients with resectable PC who underwent curative surgery, and the 1-, 2- and 3-year survival rates after surgery were 83.3, 32.4, and 19.4%, respectively. Liver metastasis was found in only one patient and no side effects of AIT were observed. CTLs stimulated by a MUC1-expressing human pancreatic cancer cell line showed a strong tumor cytotoxic activity in a MUC1-specific and MHC-unrestricted manner. AIT with stimulated CTLs significantly suppressed the postsurgical hepatic recurrence of PC. Adjuvant immunotherapy with CTLs may be useful in the postsurgical treatment of PC.

[An autopsy case of sepsis following radiofrequency ablation (RFA) for metastatic liver carcinoma after bile duct reconstruction].

An autopsy case of sepsis following radiofrequency ablation (RFA) for metastatic liver carcinoma after bile duct reconstructive operation is reported. A 72-year-old man underwent pylorus-preserving pancreaticoduodenectomy and reconstruction with the Suzuki-method (PD-III) for extrahepatic bile duct cancer in October 1998. A metastatic lesion was recognized in the liver (S3) in November 2001. Percutaneous RFA was performed for a recurrent lesion. A metastatic lesion was recognized again in the same segment in February 2002. Percutaneous RFA was performed again on February 26 and March 12. The patient was discharged without hemorrhage, infection, or hepatic failure on March 22. He complained of general fatigue on March 26. He was diagnosed with liver abscess, sepsis, acute renal failure, and disseminated intravascular coagulation, and received intensive care, but died on April 1. The autopsy revealed liver necrotic abscess at the RFA locus and multiple microabscesses of the liver, heart, and kidney.

[Immunotherapy for unresectable pancreatic cancer].

To treat unresectable pancreatic cancer, we have performed cell therapies using lymphokine-activated killer cell, cytotoxic T lymphocytes (CTLs) induced by mixed lymphocyte culture (MLC) with autologous tumor cells, and CTL recognizing MUC1 induced by MLC with an allogeneic pancreatic tumor cells line, YPK-1. CTL therapy was effective in some cases. We also performed cell therapy using MUC1 peptide-pulsed dendritic cells (MUC1-DCs) and MUC1-CTLs. This therapy was effective in one of three cases so far. Cancer peptide vaccine therapy trials for unresectable pancreatic cancer are also ongoing. Cell therapy and peptide vaccine therapy may be promising approaches for unresectable pancreatic cancer.