Poor Prognosis in Patients With Stage III Colorectal Cancer Receiving Adjuvant FOLFOX/CAPOX Therapy Is Predicted by the Presence of Many Poorly Differentiated Clusters.

BACKGROUND/AIM: Poorly differentiated clusters (PDCs) have been reported to be a useful grading system for predicting prognosis in patients with colorectal cancer (CRC). We investigated the association between the number of PDCs and prognosis in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 49 patients with stage III CRC who underwent curative surgery followed by oxaliplatin-based adjuvant chemotherapy. PDC was defined as a cluster of ≥5 cancer cells without glandular structure at the invasive front of the primary tumor. RESULTS: During the observation period, 12 patients experienced relapse. The patients were divided into two groups (<7 and ≥7 PDC groups), and receiver operating characteristic (ROC) curves were calculated [area under the curve (AUC)=0.743]. Patients with ≥7 PDCs had a much shorter relapse-free survival (RFS) than those with <7 PDCs (p<0.0001). The overall survival (OS) was also significantly worse in patients with ≥7 PDCs than in those with <7 PDCs (p<0.0001). Multivariate analysis revealed that PDC was the only significant prognostic factor measured that could predict RFS (p=0.002) and OS (p=0.0047) in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. CONCLUSION: In patients with stage III CRC treated with post-resection oxaliplatin-based adjuvant chemotherapeutic regimens, the presence of ≥7 PDCs at the invasive front of the primary tumor predicted unfavorable prognosis.

Inflammation-based Indexes Upon Adjuvant Chemotherapy Initiation as a Predictor of Relapse After Curative Resection of Colorectal Cancer With an Oxaliplatin-based Regimen.

Background/Aim: We investigated the clinical efficacy of inflammation-based indexes in predicting unfavourable relapse-free survival (RFS) in patients with stage II/III colorectal cancer (CRC) receiving oxaliplatin-based adjuvant chemotherapy. Patients and Methods: A retrospective analysis was performed on 45 patients who underwent curative resection for stage II/III CRC followed by oxaliplatin-based adjuvant chemotherapy after 8 weeks. Upon adjuvant chemotherapy initiation, all patients were evaluated for lymphocyte count (LC), neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS) and prognostic nutritional index (PNI), after which their correlation with relapse was analysed. Results: Univariate analysis identified LC <1,350/mm 3 , NLR ≥2.03, LMR <5.15, PLR ≥209, mGPS 2, and early discontinuation of chemotherapy within two months as significant risk factors for RFS. Multivariate analysis identified LMR <5.15, PLR > 209 and mGPS 2 as significant independent risk factors for unfavourable RFS. Conclusion: Measurement of LMR, PLR, and mGPS upon adjuvant therapy initiation can be a useful tool for predicting recurrence after curative surgery for stage II/III CRC.

Capecitabine Plus Bevacizumab as First-Line Therapy for Patients with Metastatic Colorectal Cancer and Poor Performance Status.

BACKGROUND: The benefit of chemotherapy for patients with metastatic colorectal cancer has not been established. METHODS: We retrospectively evaluated the effectiveness of chemotherapy with capecitabine and bevacizumab for patients with a performance status (PS) of 3. RESULTS: Seven patients were included; median age was 82 years (range, 65-91 years). Response was not ascertained; however, the disease control rate was 83.3%. Median PFS and OS were 10.0 and 25.8 months, respectively. Hand-foot syndrome was the most common toxicity observed (3 patients; 42.9%). Grade 3 toxicity was observed in 1 patient with proteinuria and 1 with hypertension. CONCLUSION: Chemotherapy using capecitabine and bevacizumab appeared to improve OFS and OS for patients with poor PS. However, care must be taken not to impose unnecessary burdens on patients with poor PS.

Laparoscopic Surgery Reduces Risk of Postoperative Complications and Non Cancer-related Survival in Patients Over 80 Years Old With Colorectal Cancer.

Background: The short- and long-term results from several reports suggest that laparoscopic surgery (LAP) for elderly patients is expected to reduce the risk of complications due to its minimal invasiveness, However, little is known about the effect of LAP on long-term prognosis aside from cancer. Patients and Methods: Eighty-five cases over 80 years old with colorectal cancer whose primary lesions were resected consecutively were enrolled. Risk factors for complications were searched using categorized clinicopathological factors. The factors for death unrelated to cancer were analyzed in patients by excluding cancer-related death. Results: Incidence of all complications, those of Clavien-Dindo grade 2 or more, and surgical site infection were significantly lower in LAP-treated patients (p=0.0343, p=0.0015 and p=0.0015, respectively). By multivariate analysis, LAP (odds ratio=0.19, 95% confidence intervaI=0.05-0.75, p=0.0177) and no pulmonary dysfunction (odds ratio=0.24, 95% confidence intervaI=0.06-0.96, p=0.0441) were significantly associated with reduced risk of complications of Clavien-Dindo grade 2 or more. LAP, no pulmonary dysfunction and Eastern Cooperative Oncology Group performance status of 0 or 1 were also significantly associated with reduced risk for death from non cancer-related causes. Additionally, LAP was significantly associated with improved survival excluding cancer-related death in patients with pulmonary dysfunction (p=0.0020) or with poor performance status (p=0.0412). Conclusion: These results suggest that fewer complications and non cancer-related deaths were achieved in very elderly patients with colorectal cancer when treated by LAP.

[Assessment of Curative Resection in Patients with Multiple Relapses of Colorectal Cancer].

We assessed the therapeutic effect of curative resection in patients with multiple relapses of colorectal cancer using the time to surgical failure(TSF)as an index. We included 24 patients who experienced recurrence after curative resection of primary colorectal cancer at our department between 1993 and 2015. Curative resection for multiple relapses was possible in these patients. The sites of recurrence included the liver, lungs, peritoneum, lymph nodes, localized, and brain in 9, 8, 3, 3, 2, and 1 patients, respectively. The relapse occurred in 2 organs in 2 patients. The TSF after curative resection of recurrent lesions was 25.6 months, with a 5-year TSF-free rate of 40.2%. The clinicopathological factors associated with poor prognosis were age B65 years at the time of recurrence, absence of distal metastasis at primary onset, and only 2 curative resections for relapses. However, there was no difference in prognosis because of the number of twice recurrent lesions. Therefore, curative resection should be proactively performed as long as feasible in colorectal cancer patients with multiple lesions or multiple relapses.

[A Case of Lung Metastases from Rectal Cancer Treated for Quite Long with FOLFIRI plus Ramucirumab as a Late Line of Therapy].

We herein report a case of lung metastases from rectal cancer treated with FOLFIRI plus ramucirumab(Ram)therapy after salvage for a long time. A 44-year-old woman underwent low anterior resection for rectal cancer. Fifteen months after the surgery, mFOLFOX6 plus bevacizumab(BV)therapy was initiated for left obturator lymph node metastases. Although the target lesion shrunk, left lung metastasis was found 36 months after the surgery. Partial resection of the lung metastasis was performed, and carbon-ion radiotherapy for pelvic recurrence was administered. Following these treatments, mFOLFOX6 plus BV therapy was administered again for multiple lung metastases 42 months after the surgery. FOLFIRI plus BV therapy, TAS- 102 plus BV therapy, and regorafenib were then administered because of the disease progression. Although the best supportive care was provided after disease progression, FOLFIRI plus Ram therapy was initiated owing to the patient's wish. Although Grade 3 hematological toxicity was observed, severe digestive symptoms were not noted. Long-term administration(approximately 1 year, 21 courses)of the drugs was possible with withdrawal. The patient died due to disease progression 66 months after recurrence. We experienced a case in which FOLFIRI plus Ram therapy after salvage line could be administered for a quite long time. It has been suggested that anti-VEGF drugs with different targets may improve the prognosis even as a late line of therapy if it is tolerable.

[Impact of Postoperative Inflammatory Status on Colorectal Cancer Prognosis].

To clarify the prognostic impact of postoperative inflammatory status, serum CRP levels on POD3 after radical resection (POD3 CRP)were evaluated as an indicator of inflammatory response after surgery in patients with colorectal cancer. Of the colorectal cancer patients who underwent radical resection at our department between 2000 and 2015, 916 patients with Stage Ⅰto Ⅳdisease were included in the analyses. The patients were divided into 2 groups according to high and low POD3 CRP levels. The POD3 CRP levels of the patients were analyzed for the 75th percentile that was 12.16mg/dL(range, 0.06- 33.78). The cancer-specific 5-year survival rate was 80.6%in patients in the high group and 90.5%in those in the low group, indicating poor prognosis in patients with high values. POD3 CRP levels were an independent prognostic factor in the multivariate analysis. It was suggested that the degree of inflammation after surgery influences the postoperative prognosis after radical resection for colorectal cancer.

[A Case of Rectal Neuroendocrine Carcinoma That Developed Two Years after Curative Resection for Sigmoid Colon Cancer].

We report a rare case ofrectal neuroendocrine carcinoma(NEC)following sigmoidectomy of sigmoid colon cancer. NEC of the rectum is a rare disease. It has an extremely poor prognosis and a high potential for malignancy with hematogenous and lymph node metastases. A 90-year-old man who had carcinoma ofthe sigmoid colon 2 years ago was found to have rectal NEC based on endoscopy findings. He underwent the Hartmann operation. Histological and immunohistochemical analyses showed NEC. Four months after the surgery, he developed local recurrence with lymph node metastasis. He was not administered chemotherapy because ofhis old age. Although the patient needed strict outpatient care, he remained symptom-free 4 months after the Hartmann operation.

[Assessment of Less Invasiveness Based on Serum CRP Level on Postoperative Day Three in Laparoscopic Surgery for Colorectal Cancer].

To evaluate the less invasiveness of laparoscopic surgery for colorectal cancer, we compared open and laparoscopic surgery for sigmoid or recto-sigmoid cancer operations undergoing the same procedures. One hundred forty-three patients curatively resected with D3 dissection were enrolled. All cases underwent the following procedure; high ligation of the inferior mesenteric artery(IMA)with median approach and double stapling technique(DST)for anastomosis. The clinicopathological factors were examined in 70 cases of open surgery(OC)and 73 cases of laparoscopic surgery(LAC). The mean age of all cases was 66(38-88)years, including 83 men and 60 women. The mean operation time was 189(82-413)minutes and the mean blood loss was 45(5-1,025)mL. Postoperative complications were reported in 45 cases including 10 cases with surgical site infection(SSI)and 10 cases with remote infection(RI). There was no difference in sex, BMI, PS, and ASA between the 2 groups; however, the patients were significantly older and the tumor maximum diameter significantly larger in the OC group. There was no significant difference in operation time but the blood loss was significantly lower in the LAC group. There were no differences in postoperative complications, first gait, WBC, and body temperature on postoperative day(POD)3, but the first flatus was earlier and the CRP level was significantly lower on POD 3 in the LAC group. There was no difference in the CRP level on POD 3 in the age, tumor diameter, and blood loss which showed a difference in the both group. Laparoscopic surgery was considered less invasive than open surgery because the serum CRP level was lower in the LAC group.

[A Case of Low-Grade Appendiceal Mucinous Neoplasm with Cecum Cancer].

The case was a 76-year-old man. He visited our hospital for a positive fecal occult blood test finding at a medical examination. A colonoscopy revealed a macroscopic, 30 mm, type-1 lesion in the cecum. We performed laparoscope-assisted ileocolic resection and D3 dissection, with a diagnosis of cecum cancer. In postoperative histopathological examination, the tumor in the cecum was diagnosed as a well-differentiated tubular adenocarcinoma. In addition, a low-grade appendiceal mucinous neoplasm(LAMN)was observed on the distal side of the appendix. The patient has survived for 9 months after surgery without recurrence. We report this case with a review of the literature.

[Efficacy of Laparoscopic Surgery for Elderly Patients with Colorectal Cancer Over 80 Years Old].

The efficacy of laparoscopic surgery for elderly patients aged over 80 years who have colorectal cancer was investigated concerning complications. Sixty-five patients over 80 years old who underwent colorectal cancer resection until January 2018 were enrolled. Factors that led to complication were analyzed retrospectively. Thirty-three men and 32 women were included, with a median age of 83 years. Forty-eight cases were located at the colon; and 17, at the rectum. The median operating time was 164 minutes, including 39 cases treated with the laparoscopic approach. Postoperative complications were observed in 28 cases(43.1%), of which 15(23.1%)had a Clavien-Dindo(CD)classification of Grade BⅡ. These cases had significantly prolonged postoperative hospital stay. Complications included 10 cases of incisional surgical site infection(SSI), 9 cases of ileus, 6 cases of melena, 2 cases of urinary infection, 2 cases of urinary disorder, and 1 case of postoperative death. Open surgery was the only significant factor associated with the incidence of CD classification of BⅡ(p=0.0330). Among the complications, the incisional SSI was reduced by laparoscopic surgery(p=0.0050). The number of laparoscopic surgeries reduced the incidence of CD classification BⅡ of complications in elderly patients aged over 80 years who had with colorectal cancer resection. The use of incisional SSI also decreased with the use of laparoscopic surgery. Laparoscopic surgery for colorectal cancer in elderly patients may lead to reduced complication rates.

[A Case of Neuroendocrine Carcinoma of the Ascending Colon That Responded Completely to Chemotherapy].

We report a case of effective treatment comprising mFOLFOX6 plus bevacizumab for neuroendocrine carcinoma of the ascending colon. A 60-year-old woman was admitted for diarrhea and abdominal pain. Colonoscopy showed a Type 2 tumor in the ascending colon. She was diagnosed with neuroendocrine cell carcinoma based on biopsy and immunostaining. CT and MRI showed liver metastasis and lymph node #12a metastasis. Right hemi-colectomy, lymphadenectomy, and partial hepatectomy were performed(T4a, N2, M1b, Stage IV). Neuroendocrine cell carcinoma(small-cell type)was finally diagnosed based on a histological examination because the nuclear fission image was 30(/10HPF)and the Ki-67 index was 42%. Three months after the surgery, multiple lymph node metastases were found using CT and MRI. mFOLFOX6 plus bevacizumab was initiated. After 4 courses of the chemotherapy, the metastases responded completely. A total of 10 courses of chemotherapy were administered. About 2 years and 6 months after the surgery, no recurrence is allowed.

[Analyses of Relapsed Cases after Oxaliplatin-Based Adjuvant Chemotherapy for Colorectal Cancer with Cur A Resection].

INTRODUCTION: There are few reports on the outcome of relapsed cases after curative resection for colorectal cancer(CRC) with adjuvant oxaliplatin-based chemotherapy. Thus, we analyzed such cases. PATIENTS AND METHOD: In total, 48 patients with CRC who received oxaliplatin-based postoperative adjuvant chemotherapy from 2012 were analyzed. The clinical course was examined in 9 cases ofrecurrence. RESULTS: Stages II, III a, and III b(1, 3, and 5 cases, respectively)were judged as recurrence in 9 cases. Metastatic sites were the lungs, local sites, liver, and peritoneum(3, 3, 3, and 1 case[s], respectively). The median time to relapse was 390 days. There were 2 cases ofwild -type RAS and 7 cases ofmutant RAS. Although R0 resection was performed in 1 case, re-relapse was recognized. Another 8 cases involved induced chemotherapy. An oxaliplatin-based regimen was administered as first-line treatment in 4 of8 cases. At present, 5 patients died, and 3 of8 cases could not progress to second-line treatment. The overall survival(OS)after relapse was 475 days, and survival more than 3 years was not observed. CONCLUSION: Recurrent cases after Cur A resection for CRC with oxaliplatin-based adjuvant chemotherapy were examined. Although the 3-year RFS and 5-year OS were relatively good, the prognosis after relapse was quite poor.

[A Case of Stage IV Rectal Cancer Achieving Long-Term Stable Disease Treated with Chemotherapy and Residual Tumor Resection].

We herein report a Stage IV case ofrectal cancer in a patient who achieved stable disease and was treated monthly with fluorouracil(FU)monotherapy plus bevacizumab(Bmab)against relapse after residual tumor resection and withdrawal because ofref usal to continue chemotherapy, even though a marked response was obtained with standard chemotherapy. A 73-year-old woman visited a former hospital in 2014, and was diagnosed with rectal cancer with liver and lung metastases (diagnosed with Rb, T3, M1b[liver, lung]cStage IV). Chemotherapy(mFOLFOX6 plus Bmab)was initiated with a consideration of conversion. After 5 courses, she moved to our hospital. Since she was not aggressive to chemotherapy from the beginning, an imaging examination was performed after 9 courses. The primary lesion and lung metastases had disappeared, and there was only one liver metastasis. Partial hepatic resection was performed to attempt chemotherapy withdrawal following informed consent. Six months after surgery with no therapy, since relapse in the rectum and lungs was confirmed, laparoscopic rectal amputation was performed to control the primary tumor. Chemotherapy containing FU monotherapy plus Bmab was reinitiated after 15 months of withdrawal because liver and lung metastases increased 5 months after rectal amputation. Two months after resuming chemotherapy, the metastatic lesion decreased in size, and the tumor marker level normalized. The same regimen is continued monthly, and the response has been maintained for 17 months(infusions of 5-FU/LV plus Bmab, 18 courses).

Subcuticular Suturing with Closed Suction Drainage for Wound Closure Following Stoma Reversal.

Incisional surgical site infection (SSI) is a leading complication of stoma reversal procedures. This retrospective study was conducted to assess the incidence of incisional SSI and other wound complications when wound closure was achieved by subcuticular suturing and closed suction drainage following stoma reversal. We analyzed data from a total of 49 patients, all of whom had undergone insertion of a 10 Fr closed suction drainage tube in the fascia, following irrigation with approximately 300 mL of physiological saline. We then performed subcuticular suturing with 4-0 monofilament absorbable sutures. The median age of our patient population (34 men and 15 women) was 68 (range, 35-84) years. Six patients had an end stoma and 43 had a loop stoma. The wound category was 'contaminated' in 18 patients, while an incisional SSI was observed in one patient (2.0%). No wound disruptions, seromas, or drain infections were evident. Our data are reliable, but our study is limited in terms of general applicability; however, the low SSI rate indicates that the procedure is acceptable. Further research into this procedure will require a randomized trial design.

[A Case of Surgery after Chemotherapy for Cecal Cancer with Onset of the Stenosis of the Colostomy].

The patient was 55-year-old woman, undergoing Hartmann operation by the sigmoid colon diverticulum perforation, 2 years later visited our hospital with abdominal pain. Although lower endoscopy and histological examination could not be performed due to stoma stenosis, we diagnosed cecal carcinoma, liver metastasis, distant lymph node metastasis from CT and PET-CT, CapeOX plus Bmabtherapy and IRIS plus Bmabtherapy were performed. After that, repeated intestinal obstruction due to exacerbated stoma stenosis, metastatic lesion increased in CT examination, furthermore the patient had hope of stoma closure, we decided to resect the primacy tumor, performed subtotal colonectomy and stoma closure. Pathological diagnosis revealed RAS wild type. After surgery, Pmabplus CPT-11 therapy was performed and the metastatic lesion was temporarily shrunk but re-exacerbated, the patient died 2 years 2 months after the first treatment started, 7 months after the primary tumor resection. In the treatment of colorectal cancer, when metastatic lesion is unresectable, chemotherapy is often carried out except when the primary tumor is symptomatic. In our case, although the primary tumor was asymptomatic, an intestinal obstruction due to stoma stenosis was developed and it was necessary to examine whether to use anti-EGFR antibody drugs, therefore we performed operation.

[Multiple Resections for Metastases from Colorectal Cancer].

PURPOSE: We analyzed to clarify an outcome of multiple resections of metastases from colorectal cancer. PATIENTS AND METHOD: Total 7 cases who underwent several resections for metastases from colorectal cancer in Saiseikai Kurihashi Hospital after 2010 were enrolled for analysis. RESULT: Age of patients at the time of the primary site resection was 67(45-78)year-old, including 4males and 3 females. Patients located at cecum/ascending/sigmoid/rectosigmoid/upper rectum were 1/1/2/2/1 respectively. Metachronous metastases were found in 5 patients. There were 1 patient for Stage I , 2 patients for Stage III a and III b each and all Stage III patients received adjuvant chemotherapy. The resected organs were 9 in lung, 8 in liver, 1 case in lymph node, local site and peritoneum and the median resected sites were 3(2-4)lesions. In 17 months median observation periods after latest resection, 5 cases have not been prolapsed including 3 cases with chemotherapy. Two cases were relapsed with unresectble status. One case died for 24 months and one case is under the chemotherapy for 12 months. Five year survival rate was 75% and 2 year prolapse free rate was 66.7%, since the relatively good prognosis was obtained by multiple resections. CONCLUSION: The cases that multiple resections with R0 were able to perform for the metastases were analyzed. Although cases which become finally to be unresectable exist, it is suggested that the relatively good prognosis might be obtained by multiple resections for metastases.

[Prognostic Relevance of Palliative Tumor Resection and Chemotherapy in Stage â £Unresectable Colorectal Cancer].

This study was conducted to evaluate the prognostic factors in patients with unresectable Stage Ⅳ colorectal cancer. One hundred and twenty-five patients who underwent either primary resection or chemotherapy for unresectable Stage Ⅳ colorectal cancer and were treated at our hospital between April 2004 and March 2014 were enrolled this study. In multiple univariate analysis, the overall survival(OS)was significantly longer in the palliative resection and chemotherapy groups. Upon dividing the 125 patients in 3 groups(the intensive chemotherapy group[L-OHP or CPT-11 regimen], extensive chemotherapy group[other regimen], and non-chemotherapy group), the intensive chemotherapy group showed significantly longer OS. Next, upon comparing the patients based on the treatment they received(surgery plus chemotherapy, surgery alone, and chemotherapy alone), the surgery plus chemotherapy group showed longer OS. With both studies combined as 5 groups, only the surgery plus intensive chemotherapy group showed longer OS. This is shown in unresectable Stage Ⅳ cancer patients, wherein resection of the primary lesion in addition to intensive chemotherapy contributes to longer OS.

[A Case of Ascending Colon Cancer with Hepatic Metastases Showing Remarkable Efficacy of CapeOX plus Bevacizumab].

We report a case of ascending colon cancer with hepatic metastases that was treated by CapeOX plus bevacizumab with remarkable efficacy. A 40-year-old female patient presented with a medical history of surgery for resection of right breast cancer4 years ago, left-sided transverse colon 2 years ago, and right ovarian cancer 6 months ago. Follow-up computed tomography(CT)found wall thickening from the ascending colon to cecum. She was diagnosed with an ascending colon cancer by colonoscopy, and underwent right hemicolectomy. One month after the surgery, her serum marker carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels were high. She was diagnosed with unresectable multiple hepatic metastases by CT 2 months after the surgery. Her tumor was epidermal growth factor receptor(EGFR)- positive and wild-type for RAS; she received 4 courses of CapeOX plus bevacizumab. Thereafter, liver metastases were remarkably decreased in size, and she could undergo central bisegmentectomy. Pathology examination revealed no tumor and that the center of the tumor was changed to necrotic tissue and the surrounding area was changed to fibrous tissue and lymphocyte infiltration. The patient is disease-free since the last operation.

[Treatment Outcomes of Curative Resection for Colorectal Cancer with Synchronous Liver Metastasis].

The aim of this study was to clarify prognosis for curative resection performed for cases of colorectal cancer with synchronous liver metastasis and to use the findings as future treatment indices. Subjects comprised 61 patients who underwent curative resection at our hospital for colorectal cancer accompanied by synchronous liver metastasis between 1996 and 2014. The degree of liver metastasis was H1 for 47 cases and H2 for 14 cases. The Grade of liver metastasis was A for 29 cases, B for 18 cases, and C for 14 cases. Liver resection was performed simultaneously with that of the primary lesion for 33 cases, and after that of the primary lesion for 28 cases. The post-curative resection survival period was 58.0 months, and the 5-year survival rate was 49.9%. In terms of the relationship between prognosis and clinicopathological factors, prognosis was found to be poor when the wall depth of the primary lesion was pT4 and when the liver metastasis Grade was B or C. Meanwhile, prognosis did not differ depending on the timing of liver metastasis resection, whether chemotherapy was performed after liver resection, and whether curative resection was performed for initial occurrence only or recurrence resection was performed. The results indicated that for cases of colorectal cancer with synchronous liver metastasis, primary lesion wall depth and liver metastasis Grade were prognostic factors, and that the treatment strategy did not necessarily have to consider resection timing.