Nucleic Acid Metabolizing Enzyme Levels Predict Chemotherapy Effects in Advanced and Recurrent Colorectal Cancer.

BACKGROUND: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) predict the effects of fluoropyrimidine. However, the effects of FOLFOX therapy from the perspective of fluorouracil plus leucovorin (FL) remain underexplored. Hence, the relationship between mFOLFOX6 therapy (mFOLFOX6) and therapeutic efficacy was evaluated in patients with advanced/recurrent colorectal cancer (CRC). METHODS: Correlations between TS and DPD and primary and metastatic lesions in recurrent CRC were analyzed. Univariate and multivariate analyses of TS and DPD in combination with response rate (RR), progression-free survival (PFS), and overall survival (OS) were performed. RESULTS: A positive correlation between DPD and primary and metastatic lesions; correlations between TS and RR, DPD and RR, and PFS and OS; and significant differences for RR and DPD and TS, PFS and DPD, and OS and DPD were obtained. CONCLUSION: Nucleic acid metabolizing enzymes in primary lesions can be used to predict mFOLFOX6 efficacy in patients with recurrent CRC.

[A Case of Diffuse Large B-Cell Lymphoma of the Testis, Which Also Developed in the Rectum after Resection of a Large B-Cell Lymphoma].

A man aged 65 years had undergone high orchidectomy of the right testis for diffuse large B-cell lymphoma(DLBCL) occurring primarily in the testis 11 months before. Although he was referred to another hospital for postoperative chemotherapy, he refused the treatment by self-judgement. For 1 month, he had been experiencing melena and anal pain, so he visited our department in June. Rectal palpation revealed a sub-circumference tumor palpable from the anal margin, in which a part protruded outside the anus. CT revealed a sub-circumference hypertrophic wall from the rectal Ra to the anus and intramural enlarged lymph nodes, without metastases to the other organs. Systemic gallium scintigraphy detected a strong concentration in the rectum. The endoscopic examination of the inferior region revealed a circumference type 2 tumor at Rb, and biopsy revealed DLBCL. Clinically, this case was considered a testoid DLBCL with rectal metastasis. Therefore, we performed laparoscopic rectal amputation in July, XX. sT3N1b, cM0. The postoperative course was uneventful. After the patient was discharged from our department, he received chemotherapy at another hospital. At present, 4 years 0 month postoperatively, the patient condition is favorable without recurrence. When perforation occurs in gastrointestinal DLBCL, the start of chemotherapy is delayed and the primary lesion worsen. Therefore, we performed surgical therapy first. Such cases must be evaluated for metastases or new lesions carefully.

[A Case of Isolated Metachronous Splenic Metastasis after Rectal Cancer Surgery].

A 50-year-old woman underwent laparotomic anterior resection(D3)and total hysterectomy with bilateral adnexectomy (type 2, 3.0×4.5 cm, pT4a[SE], N1a, M1c2[ovary and peritoneum], H0, P1, PUL0, stage Ⅳc, tub2>por, Cur B)for ovarian metastasis from rectal cancer in June 20XX. During the outpatient visit in May, 2 years and 11 months after surgery, a splenic tumor was found on abdominal contrast-enhanced CT, without distant metastasis in other organs. In July 20XX, laparoscopic splenectomy was performed for suspected splenic metastasis of rectal cancer. The specimen of the resected tumor showed pathological findings consistent with metastasis of rectal cancer. Currently, the patient is being followed up without any sign of recurrence. Herein, we report a rare case of isolated metachronous splenic metastasis, whose associated prognosis might be improved by surgical treatment, in reference to the literature.

[A Case of Sigmoid Colon Neuroendocrine Cell Carcinoma Discovered by Defecation Disorder].

A 65-year-old man presented to our hospital with a chief complaint of abdominal pain during defecation. Abdominal contrast-enhanced CT showed circumferential wall thickening with contrast effects in the sigmoid colon, and multiple metastases in the liver. Colonoscopy revealed a type 2 colon tumor that was obstructing the passage. A diagnosis of sigmoid colon cancer and multiple liver metastases was made based on laparoscopic sigmoidectomy plus D3 dissection. Pathologically, the resected specimen was diagnosed as colorectal neuroendocrine cell carcinoma(NEC)that was positive for synaptophysin and CD56. Postoperatively, 8 courses of FOLFOX plus bevacizumab(BV)therapy were administered, but CT showed remarkable increase in liver metastasis, and he died 5 months after the operation. Colorectal NEC is a very rare disease, for which no chemotherapy has been shown to be effective. Since we encounterd a case of sigmoid colon NEC with multiple liver metastases that followed a rapid course, we have presented it along with a literature review.

Long-Term Survival After Multidisciplinary Treatment Including Surgery for Metachronous Metastases of Small Intestinal Gastrointestinal Stromal Tumors after Curative Resection: A Case Report.

BACKGROUND Currently, 3 molecular targeted drugs are available for the treatment of unresectable and recurrent gastrointestinal stromal tumors (GISTs), and result in improved prognoses and rare occurrence of bone metastases. However, there is no established treatment guideline for bone metastases of GIST. CASE REPORT The patient was a 56-year-old male who was diagnosed with leiomyosarcoma in 1997. Partial resection of the small bowel was performed. As part of post-operative follow-up in 2004, a computed tomography scan showed metastatic lesions in the liver and the right femoral neck. Accordingly, partial hepatectomy was performed, followed by artificial femoral head replacement. In 2006, bone metastases were detected in the sternum, cervical and thoracic vertebra, and the right upper arm; therefore, the patient was subjected to radiotherapy. However, further histopathological examination revealed positive findings for CD34+ and KIT cells, prompting a diagnosis of GIST. Imatinib was started. The disease remained stable. However, in 2010, metastasis to the right ilium was detected, after which there was an increase in metastatic lesions in the thoracic vertebra, prompting a diagnosis of progressive disease. Thus, treatment with sunitinib was initiated. In 2012, the patient experienced spinal paralysis due to metastasis in the eighth thoracic vertebra. In 2013, metastases in the right ilium, lungs, and liver were detected. In 2014, the patient died. CONCLUSIONS Multidisciplinary treatment via radiotherapy and surgery for GIST with bone metastases indicates the possibility of extending the overall survival further.

[A Case of Diverticular Perforation of Sigmoid Colostomy during FOLFIRI plus BevacizumabTreatment].

A 61-year-old man with a diagnosis of rectal cancer underwent assisted laparoscopic rectal amputation. Recurrence occurred, and treatment with FOLFIRI plus bevacizumab was initiated at our department. After 12 treatment courses, he developed abdominal pain at home. Emergency surgery was performed for the stoma perforation. We confirmed the diverticular perforation in the resected specimen. In our case, we found a para-stoma hernia and considered it to be the cause of perforation together with bevacizumab administration. Molecular-targeted drugs contribute to improving treatment outcomes in malignant tumors, but specific adverse events such as perforation have been reported. In addition, as causes of sigmoid colon perforation such as that of the stoma, cases associated with intestinal operation, constipation, and para-stoma hernia are suggested. In our case of hyperpolarization due to a para-stoma hernia, administration of bevacizumab was considered the cause of the perforation. This was a case that could be rescued with surgery.

[A Case Where Function Preservation Was Possible for Quadruple Cancer Metastasis].

The patient was a 69-year-old man visited our hospital because of fecal occlt blood test at medical checkup and diagnosed with rectal cancer and gastric cancer. The patient underwent super low anterior resection for rectal cancer cStage III b and underwent endoscopic submucosal dissection(ESD)for early gastric cancer. In 1 year after surgery the patient had recurrence of gastric cancer after ESD and recurrent gastric cancer was additionally resected. In 1 year and 4 months after surgery pulmonary metastasis was recognized and the patient underwent pulmonary segmentectomy. In 5 years after surgery renal cell carcinoma was recognized and the patient underwent partical renal excision. In 8 years after surgery esophagus cancer was recognized and the patient underwent radical chemoradiationtherapy and completed local complete remission. Current the patient is alive without relapse. We report a case where function preservation was possible for quadruple cancer by appropriate preoperative and postoperative examination and appropriate treatment.

[Long-Term Survival of a Patient with Mediastinal Lymph Node Metastasis Treated with Chemo-Radiotherapy after Surgery for Cecal Cancer].

In June 1997, the patient underwent an operation for cecal colon cancer pStage II .I n May 1999, a liver metastasis at S6 was detected and the patient received a partial liver resection.In April 2004, a liver metastasis in S4 was detected and another partial liver resection was performed.In November 2008, he complained of hemoptysis and cough.The chest CT examination showed lymph node metastases in the mediastinum that invaded the left main bronchus.We performed chemo-radiotherapy for local control from January 2009. Because the lymph nodes were reduced remarkably and clinical complaints disappeared, we administrated a mFOLFOX6 regimen from June.We recognized the effect of treatment to be a complete response.In February 2014, we detected a lymph nodes recurrence around a right pulmonary artery.We performed chemo-radiotherapy again because the patient declined surgery.However, lymph node metastases did not completely respond.We then performed chemotherapy 30 times using a FOLFIRI plus panitumumab regimen.On PET-CT, the recurrent lesion did not show a hot spot.We experienced a case that responded to chemo-radiotherapy for long-term control of lymph node recurrence.

[A Case of Neuroendocrine Carcinoma with Liver Metastasis Treated with Multimodality Therapy and Leading to Complete Response].

A 79-year-old man with cStage II A(T2N1H0P0CYXM0)advanced gastric cancer in angle. Distal gastrectomy was performed and liver metastasis was recognized during the operation. The pathological diagnosis was shown as neuroendocrine carcinoma(NEC). Chemotherapy(S-1/cisplatin[CDDP]: 1 course, etoposide/CDDP: 5 courses)was administered. After chemotherapy, liver metastasis disappeared for 9months.

[Stereotactic Body Radiotherapy for Liver Metastasis of Gastric Cancer].

Case 1: A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5). After the operation, we administered chemotherapy. After that, we performed partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared as 2 lesions in February 2009. Thus, we administered another type of chemotherapy. The effect of the chemotherapy was not favorable. Therefore, SBRT was performed for the liver metastases in December. After SBRT, he did not present with any recurrent tumors. Case 2: A 67-year-old woman underwent distal gastrectomy in March 2015. In August 2015, hepatic metastasis(S5 single shoot)was confirmed. Although chemotherapy was administered and SD was continued, it was ceased due to the patient's request. Thus, SBRT was performed in July 2016. However, from October 2016, multiple liver metastases developed and she died in January 2017.

[Treatment Outcome of Intersphincteric Resection in Tokyo Medical University Hospital].

PURPOSE: This study aimed to consider the oncological validity of intersphincteric resection(hereinafter referred to as ISR) performed at Tokyo Medical University Hospital, as well as associated dysfunction. SUBJECTS: Subjects included 73 cases in which ISR was performed at Tokyo Medical University Hospital between November 2004 and January 2016. RESULTS: The 5- year overall and relapse-free survival rates for cases with Stage 0 to III were 90.4% and 77.3%, respectively. Two cases with recurrence among cases with Stage I were both of local recurrence.The Wexner score of the cases 12 months after closure of ileostomy was 4.2±2.5 points, while it had not been performed for the other 10 cases. DISCUSSION: In consideration of the relatively preferable local control observed with ISRs that had been performed at our hospital, defecation disorder was considered to be within an allowance.However, there remained a problem that closure of ileostomy could not be performed for 10% of the cases. CONCLUSION: ISR was believed to be valid as a sphincter-preserving procedure in consideration of the function and curability.

[Efficacy of Partial Resection for Stomach Cancer in the Elderly].

We examined the effectiveness of partial gastrectomy in the elderly. Twelve patients who underwent partial gastrectomy for gastric cancer in our hospital had an average of 2.75 comorbidities before surgery. Two patients relapsed, and 2 patients died from other diseases. The depth of the gastric tumor was T2 in patients with recurrence. Partial gastrectomy should be considered carefully for advanced stage cancer. There were only small changes in weight, PS, and nutrition before and after surgery, suggesting that partial gastrectomy is effective.

[Pathological Complete Response in 3 Patients with Esophageal Cancer Treated with Neoadjuvant Chemoradiation Therapy].

Neoadjuvant chemotherapy(NAC)for esophageal cancer is standard in Japan. However, the value of neoadjuvant chemoradiation therapy(NACRT)is unknown. Thirteen patients with cStage II and III squamous cell carcinoma of the esopha- gus were treated with NACRT(CDDP 70mg/m2/day on day 1, 5-FU 70 mg/m2/day on days 1-4, radiation 30 Gy/15 Fr). We report 3 pathological CR cases and 10 non-CR cases of esophageal cancer. Between the CR and non-CR group there was no difference in the incidence of postoperative complications. No serious adverse events were observed. There were no significant differences in OS and RFS. Five cases relapsed in the non-CR group. There were no relapsed cases in the CR group.

[A Case of Gastric Cancer Responding to Neoadjuvant Chemotherapy Leading to Histological Change to Grade 3].

A 70-year-old man with cStage III A(cT3N2H0P0CYXM0)advanced gastric cancer in the lesser curvature with esophageal invasion and bulky lymph nodes was treated with S-1/CDDP. After 4 courses of chemotherapy, the tumor and lymph nodes were found to be reduced in a CT examination. Total gastrectomy with lymph node dissection(D2)was performed. Histopathological examination revealed no cancer cells in the stomach or lymph nodes, indicating Grade 3.

[Efficacy of Radiation Therapy for Esophageal Cancer with Bone Metastases].

We retrospectively considered the validity of radiotherapy for patients with bone metastases from esophageal cancer. Eight patients have received radiotherapy in our hospital since 2007. The median age of the patients was 63 years, with 5 men and 3 women. Bone metastatic sites were 4 to the vertebrae, 3 to the ribs, 3 to the femur and 1 each to the humerus, ulna, and radius, respectively. All of the patients had other unresectable sites of metastasis. Radiotherapy reduced pain of 3 patients of PS 1 clearly. Median survival time from the start of radiation therapy was 50 days. When PS was relatively good, the possibility of easing pain and improving QOL was suggested by our data. There is a possibility that radiation therapy for patients with bone metastases from esophageal cancer can improve the QOL and alleviate pain.

A case of a gastrointestinal stromal tumor with skeinoid fibers of the sigmoid colon.

An 80-year-old man was diagnosed with rectal cancer and underwent Hartmann's procedure. Although no tumors were identified during the preoperative examination, gross examination of the resected specimen incidentally revealed a submucosal tumor that was 9 mm in diameter at the oral side and located in the proximal stump of the specimen from the sigmoid colon. We suspected a concurrent gastrointestinal stromal tumor (GIST) and performed a histopathological examination. An L-shaped nodular lesion measuring 9 × 6 mm was histologically composed of a patternless proliferation of spindle cells intermingled with eosinophilic globules. Cellular atypia, prominent mitotic figures and necrotic foci were not observed in the nodule. The spindle cells were positive for CD34, CD117 and vimentin, but negative for CD56, smooth muscle actin and S-100 protein. MIB-1 positivity was estimated to be as low as approximately 1-2%. Electron microscopy showed a bundle of wool-like fibers with a periodicity of approximately 40 nm. We therefore considered the lesion to be a low-risk GIST with skeinoid fibers in the large intestine. Although numerous previous reports have reported skeinoid fibers in the stomach and small intestines, there have been only 9 cases (including the present case) of skeinoid fibers in the large intestine.

Examination of prognostic factors in patients undergoing surgery for colorectal perforation: a case controlled study.

OBJECTIVE: To determine if the POSSUM, SOFA, MPI, and SAS scores provide a better measure of severity for patients with prognostic factors undergoing surgery for colorectal perforation. SUBJECTS: Fifty-nine patients who underwent surgery between 1996 and 2012. METHODS: We retrospectively reviewed background factors, blood and physiological test results, and intraoperative findings of patients who survived and those who died. We also compared the POSSUM, SOFA, MPI, and SAS scores. Multivariate analysis was performed for factors that were significant by univariate analysis, and selected factors were used to produce a predictive prognostic model. RESULTS: Univariate analysis revealed significant differences in age, anticoagulant/steroid administration, serum creatinine level, PF ratio, base excess (BE), chest radiography, pulse rate, and severity of peritoneal soiling. Age, serum creatinine level, pulse rate, and severity of peritoneal soiling were selected for multivariate analysis; only pulse rate was significantly different. There were significant differences between the two groups in POSSUM PS, OSS, SOFA, and MPI scores, and a comparison in terms of the ROC curve showed that our model had the highest peak; the area under the curve was 94.8% compared with 70-80% for the other systems, suggesting that our model is better than those systems. CONCLUSIONS: POSSUM and SOFA are valid methods of evaluating risk from colorectal perforation, but our study revealed addition risk factors: (1) the PF ratio and BE, which are not included in POSSUM; (2) the pulse rate and severity of peritonitis, which are not included in SOFA; and (3) anticoagulant/steroid hormone administration.

[Evaluation of esophageal cancer treatment for patients aged over 80 years].

We examined the effectiveness of chemoradiotherapy for esophageal cancer patients aged 80 years or older, 9 of whom were treated after 2010. Treatment consisted of cisplatin 35 mg/m² (day 1 and 29) and 5-FU 350 mg/m² (days 1-4 and 29- 32) combined with 50.4 Gy radiotherapy (1.8 Gy/day, 5 days/week, days 1-42). We administered 50% of the normal dose of chemotherapy. Median survival was 387 days, and there were 6 PRs, 1 SD, and 2 PDs. The toxicities related to the chemoradiotherapy were manageable (7 patients had toxicities worse than Grade 2, of whom 6 died and 3 were alive at the time of reporting). This treatment may be effective and safe for elderly esophageal cancer patients.

[The efficacy of neoadjuvant chemotherapy with S-1/CDDP (SP) to the patients with large type 3 and type 4 gastric cancer].

Here, I examined the efficacy of neoadjuvant chemotherapy( NAC) with S-1/CDDP( SP) in my hospital. The subjects were 8 patients with advanced gastric cancer who had undergone NAC since 2007 (7 men and 1 woman; median age, 70 years). The staging before the treatment was Stage II A: 1 patient, II B: 2 patients, III B: 3 patients, III C: 1 patient, and IV: 1 patient. The macroscopic type of 3 and 5 patients was large type 3 and type 4, respectively. Gastrectomy was performed following the NAC with SP. The NAC response rate was 62.5%. In the histological response criteria, 1 patient was grade 0, 2 patients were grade 1a, 2 patients were grade 1b, and 3 patients were grade 2. Adverse events following the NAC were in the acceptable range. We noted that the presence of Stage IV or grade 0 histological response criteria to NAC indicated poor prognosis. Thus, I believe that preoperative surgery after NAC in Stage III gastric cancer should be considered to be curative.

Correlations of clinicopathological factors with protein expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase and orotate phosphoribosyltransferase in colorectal cancer.

BACKGROUND: Expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) have been reported to be associated with tumor response to 5-fluorouracil (5-FU). METHOD: We investigated correlations of clinicopathological factors with protein expression levels of TS, DPD, OPRT in colorectal cancer (CRC). The subjects were 202 patients who had undergone CRC resection. RESULT: There was a negative correlation between DPD and OPRT protein levels, but no correlation of TS levels with either OPRT or DPD levels. The DPD levels in women was significantly lower than that in men. The DPD level was significantly lower in colonic tumors than in rectal tumors, while the OPRT level was significantly higher in colonic tumors than in rectal tumors. The TS level did not correlate with any clinicopathological factors. CONCLUSION: DPD and OPRT protein levels in CRC suggest that female gender and colonic tumors are positive prognostic factors in patients who receive chemotherapy with 5-FU.