Spontaneous regression of advanced transverse colon cancer with deficient mismatch repair: a case report.

BACKGROUND: Spontaneous regression (SR) of cancer occurs in 1 in 60,000-100,000 patients. This phenomenon has been reported in almost all cancer types, most commonly neuroblastoma, renal cell carcinoma, malignant melanoma, and lymphoma/leukemia. However, SR in colorectal cancer (CRC) is extremely rare, particularly in advanced cases. Hence, this report describes a very rare case of spontaneous regression of advanced transverse colon cancer. CASE PRESENTATION: A 76-year-old female with anemia was diagnosed with a type II well-differentiated adenocarcinoma in the middle transverse colon. Two months later, a second colonoscopy examination was performed for preoperative marking, and it revealed tumor shrinkage and a shift to type 0-IIc morphology. Endoscopic tattooing was then performed, followed by a laparoscopic partial resection of the transverse colon with D3 lymph node dissection. However, the resected specimen contained no tumor, and colonoscopy showed no tumor remnants in the remaining colon. Histopathological examination revealed mucosal regeneration and a mucus nodule in between the submucosal and muscular layers, with no cancer cells detected. Immunohistochemical analysis revealed the loss of MutL homolog 1 (MLH1) and postmeiotic segregation increased 2 (PMS2) expression in the cancer cells of biopsied specimens, suggesting deficient mismatch repair (dMMR). The patient continues to be followed up until 6 years postoperatively, and no recurrence has been observed. In this study, we also reviewed similar reported cases of spontaneous regression of cancer involving dMMR. CONCLUSION: This study presents a rare case of spontaneous regression of advanced transverse colon cancer wherein dMMR is strongly involved. However, further accumulation of similar cases is needed to elucidate this phenomenon and to develop new treatment strategies for CRC.

[A Case of Intrahepatic Cholangiocarcinoma in Contact with the Gastroduodenal Anastomosis in Which Proton Beam Therapy Was Performed after Placement of an Absorbable Spacer].

Chemotherapy is the standard therapy for unresectable intrahepatic cholangiocarcinoma(ICC), but chemotherapy is not efficacious. Proton beam therapy(PBT)has been covered by Japanese health insurance for ICC since 2022, and the number of cases is expected to increase. In some cases, irradiation is difficult due to the close proximity of the gastrointestinal tract to the tumor. We report our management of a patient with ICC close to the gastrointestinal tract. The patient was a 69-year- old woman with a history of distal gastrectomy and Billroth-Ⅰ reconstruction for gastric cancer. A CT scan showed a tumor in liver S3; a biopsy revealed ICC. Because the tumor was in contact with the gastroduodenal anastomosis, we placed an absorbable spacer and performed PBT. After the treatment, the tumor shrank slightly. Although the liver is anatomically adjacent to the digestive tract, the placement of absorbable spacers facilitates performing PBT without adverse events, and is thus considered a useful treatment.

Cancer cell­induced tissue inhibitor of metalloproteinase­1 secretion by cancer­associated fibroblasts promotes cancer cell migration.

Cancer­associated fibroblasts (CAFs) are one of the major components of the cancer stroma in the tumor microenvironment. The interaction between cancer cells and CAFs (cancer­stromal interaction; CSI) promotes tumor progression, including metastasis. Recently, the tissue inhibitor of metalloproteinase­1 (TIMP­1) was reported to promote cancer cell migration and metastasis, which is contrary to its anticancer role as an inhibitor of matrix metalloproteinase. Moreover, CAF­derived TIMP­1 is reported to regulate CAF activity. In the present study, we investigated the effect of TIMP­1 on colon cancer cell migration in vitro. The TIMP­1 secretion levels from the CAFs and cancer cell lines were comparatively measured to determine the main source of TIMP­1. Furthermore, the effect of CSI on TIMP­1 secretion was investigated using the Transwell co­culture system. Cancer cell migration was evaluated using the wound­healing assay. The results demonstrated that TIMP­1 promoted the migration of LoVo cells, a colon cancer cell line, whereas TIMP­1 neutralization inhibited the enhanced migration. The TIMP­1 levels secreted from the cancer cells were approximately 10 times less than those secreted from the CAFs. TIMP­1 secretion was higher in CAFs co­cultured with cancer cells than in monocultured CAFs. Furthermore, the migration of LoVo cells increased upon co­culturing with the CAFs. TIMP­1 neutralization partially inhibited this enhanced migration. These results suggest that CAFs are the primary source of TIMP­1 and that the TIMP­1 production is enhanced through CSI in the tumor microenvironment, which promotes cancer cell migration.

The expression of carcinoembryonic antigen mRNA in the lavage of the dissected area of the lateral lymph nodes influences the lateral recurrence of lower rectal cancer.

PURPOSE: To determine whether or not migrating cancer cells are present on the surgical plane after lateral lymph node dissection (LLND) for lower rectal cancer and related to lateral recurrence (LR), we evaluated the lavage of LLND areas by reverse-transcription polymerase chain reaction (RT-PCR) to check the expression of CEA mRNA in the residual cancer cells. METHODS: Thirty patients who underwent curative LLND were enrolled. Lavage was collected after LLND and subjected to RT-PCR to detect CEA mRNA. The median follow-up to check for recurrence was 31.4 months. RESULTS: CEA mRNA was detected in 9 of the 46 dissected areas. Based on the receiver operating characteristic curves, the cut-off value of PCR was set at 0.025. This cut-off point classified five patients into the high-expression group for CEA mRNA. During follow-up, LR developed in 1 of 40 low-expression areas of CEA mRNA and 3 of 6 high-expression areas. The LR rate was higher in the high-expression group than in the low-expression group (p = 0.015). A multivariate analysis showed that the high expression of CEA mRNA was likely an independent prognostic factor of LR. CONCLUSION: The expression of CEA mRNA in the lavage of LLND areas indicates the presence of residual cancer cells that cause LR.

Eicosapentaenoic acid suppresses angiogenesis via reducing secretion of IL­6 and VEGF from colon cancer­associated fibroblasts.

Eicosapentaenoic acid (EPA) improves interleukin (IL)­6 hypercytokinemia in patients with advanced cancer due to its anti­inflammatory effects. This EPA mechanism has been revealed to lead to several anticancer effects. While the effects of EPA on cancer cells have been investigated, particularly in terms of angiogenesis, its effects on the tumor stroma remain unclear. In the present study, the authors clarified the role of EPA in cancer angiogenesis against colon cancer­associated fibroblasts (CAFs) from the colon stroma. With established human CAFs and normal fibroblasts from colon stroma (NFs), the authors evaluated IL­6 and vascular endothelial growth factor (VEGF) secretion with or without EPA treatment using ELISA. The signal inhibition of mitogen­activated protein kinase (ERK) in CAFs by EPA was evaluated using western blotting. In vitro anti­angiogenesis effects were evaluated by the angiogenesis assay on Matrigel using human umbilical vein endothelial cells (HUVECs) cultured with the supernatant obtained from CAF cultures with or without EPA. IL­6 secretion was greater from CAFs compared with that from NFs and stimulation with lipopolysaccharide (LPS) resulted in greater IL­6 secretion from the two fibroblast types compared with that from fibroblasts without LPS stimulation. While LPS stimulation increased VEGF secretion from the two fibroblast types, EPA decreased IL­6 and VEGF secretion from CAFs. Western blotting revealed that the addition of 30 µM EPA inhibited the ERK phosphorylation signal in CAFs. Furthermore, the angiogenesis assay with Matrigel revealed that the CAF culture supernatants treated with EPA suppressed tubular formation in HUVECs. These reductions may have been caused by the inhibition of ERK phosphorylation by EPA. Thus, EPA reduces cancer angiogenesis associated with CAFs. Additional studies will be needed to clarify the continuous anti­angiogenetic effect of chemotherapy using angiogenesis inhibitors (e.g. bevacizumab and aflibercept) in conjunction with or without EPA, and the clinical usage of EPA in conjunction with chemotherapy in vivo.

Laparoscopic extraperitoneal sigmoid colostomy using the totally extraperitoneal hernia repair technique after abdominoperineal resection for rectal cancer.

Stoma creation through the extraperitoneal route reportedly reduces the risk of parastomal hernia and stomal prolapse after abdominoperineal resection (APR) for rectal cancer. We describe a new technique for laparoscopic extraperitoneal sigmoid colostomy following APR. After the rectus abdominis muscle is separated, Lap ProtectorTM and EZ AccessTM devices are placed. An extraperitoneal stoma tunnel is created laparoscopically as much as possible. Next, the peritoneum is separated from the inside of the abdominal cavity, and the extraperitoneal tunnel is opened. At the time of writing, we had performed laparoscopic extraperitoneal sigmoid colostomy in eight patients, without any complications or conversion to the conventional procedure. Thus, laparoscopic extraperitoneal sigmoid colostomy is a useful and safe technique for the laparoscopic creation of an extraperitoneal stoma tunnel after APR.

No inflammatory benefit obtained by single-incision laparoscopic surgery for right hemicolectomy compared with conventional laparoscopy.

PURPOSE: We evaluated the perioperative inflammatory mediators in a right hemicolectomy performed with single-incision laparoscopic surgery (SILS) and traditional multi-port laparoscopic surgery (MLS) to compare the postoperative inflammatory response and feasibility of SILS with that of MLS. METHODS: In this retrospective study, we enrolled 56 consecutive colorectal cancer patients who underwent right hemicolectomy prospectively. Twenty patients underwent SILS, and 36 underwent MLS. The preoperative and postoperative levels of plasma vascular endothelial growth factor (VEGF), serum interleukin-6 (IL-6), and C-reactive protein (CRP) as well as the number of platelet cells were measured in all patients. The operation duration, number of harvested lymph nodes, length of the resected bowel, blood loss, and duration of hospital stay were also compared between the two groups. RESULTS: Neither SILS nor MLS had any conversion cases. The operation duration was longer for MLS than for SILS. Blood loss tended to be lower among patients who underwent SILS than among those who underwent MLS. However, the number of harvested LNs was significantly lower with SILS than with MLS. In both pre- and postoperative blood examinations, there was no marked difference in inflammatory mediators between MLS and SILS. CONCLUSION: There was no systemic inflammatory advantage associated with SILS compared with MLS.

Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer.

Apigenin is a natural flavonoid that exhibits anti-proliferative activity and induces apoptosis in various types of cancer, including colon cancer. The aim of the present study was to determine the mechanism underlying the apoptosis-inducing effect of apigenin in colon cancer. Apigenin reduced the proliferation of colon cancer cell lines, stimulated the cleavage of PARP and induced apoptosis in a dose-dependent manner. Apigenin treatment also suppressed the expression of the anti-apoptotic proteins Bcl-xL and Mcl-1. Small interfering RNA was used to knockdown Bcl-xL and Mcl-1 expression alone and in concert, and the proliferation and apoptosis of cancer cells were subsequently measured. The knockdown of Bcl-xL and Mcl-1 expression together markedly suppressed cell proliferation and induced apoptosis. Apigenin treatment also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which targets Bcl-xL and Mcl-1. The results of the current study therefore determined that apigenin induces the apoptosis of colon cancer cells by inhibiting the phosphorylation of STAT3 and consequently downregulates the anti-apoptotic proteins Bcl-xL and Mcl-1.

Spontaneous perforation of pyometra presenting as acute abdomen and pneumoperitoneum mimicking those of gastrointestinal origin.

Gastrointestinal (GI) perforation accounts for over 90% of acute abdomen and pneumoperitoneum. The presence of pneumoperitoneum secondary to spontaneously perforated pyometra is an interesting yet confusing finding given the absence of gastrointestinal (GI) perforation, because pyometra is more common in postmenopausal women. We report an instructive case of diffuse peritonitis caused by spontaneous perforation of pyometra. A 70-year-old postmenopausal female was admitted to surgical emergency with signs of diffuse peritonitis. After resuscitation, an emergency laparotomy was performed because of suspicion of GI perforation. At laparotomy, about 2,000 mL of purulent fluid was found to be present in peritoneal cavity, while GI tract was intact. A rent with a diameter of 5 mm was found on anterior fundus of uterus. A total abdominal hysterectomy with a bilateral salpingo-oophorectomy was performed. Despite intensive care and a course of antibiotics, the patient died of multiple organ failure resulting from sepsis on postoperative day 16. Our case illustrates the importance of clinical knowledge of acute gynecological diseases, which are not uncommonly encountered by the general surgeon. Moreover, good appreciation of pelvic anatomy and close collaboration with gynecology and GI surgery colleagues is essential as operative intervention is often required.

[A case of double cancer of sigmoid colon cancer with lung metastases, peritoneal dissemination and early gastric cancer responding to S-1].

A 73-year-old man was referred to our hospital with complaints of constipation and defecation caused by a sigmoid colon tumor. After examination, he was diagnosed as sigmoid colon cancer with lung metastasis, peritoneal dissemination and early gastric cancer. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative day 20, S-1 (100 mg/body for 4 weeks followed by 2 drug-free weeks) treatment was started. After 13 courses of treatment, gastrointestinal fiberscope revealed that the gastric cancer was remarkably reduced, and after 16 courses, computed tomography revealed that the lung metastasis was remarkably reduced. Although after 12 courses, elevation of bilirubin, the treatment could be possible to continued on a lowered dose of S-1 from 100 mg to 80 mg/body. Twenty-four months after the operation, good control of cancer has been maintained, and the treatment is continuing. S-1 treatment was proved effective for double cancer of the advanced colorectal cancer and the gastric cancer.