[A Case of Early Gastric Cancer with Esophageal Hiatal Hernia Treated by Laparoscopic Gastrectomy for Cancer and Repair of Hiatal Hernia].

We report a successful case of gastric cancer with esophageal hiatal hernia treated by laparoscopic surgery. The patient was a 75-year-old woman who was referred to our hospital with a diagnosis of early gastric cancer with esophageal hiatal hernia. Laparoscopic distal gastrectomy with lymph node dissection and esophageal hiatal hernia repair using primary suture method without mesh were performed simultaneously. She had a good postoperative course without the recurrence of both cancer and hernia.

[A Case of Synchronous Papillary Thyroid Cancer and Breast Ductal Cancer].

Occurrences of thyroid cancer and breast cancer metachronously or synchronously are common for women. Explanations for these associations include detection bias, shared hormonal risk factors, and genetic susceptibility, but the etiology behind specific associations is not elucidated well. The importance of the relationship between breast and thyroid cancer will continue to become evident and physicians should be aware of this association in caring for thyroid and breast cancer survivors. We report a case of synchronous papillary thyroid cancer and breast ductal cancer.

Identification of a Novel Bone Marrow Cell-Derived Accelerator of Fibrotic Liver Regeneration Through Mobilization of Hepatic Progenitor Cells in Mice.

Granulocyte colony stimulating factor (G-CSF) has been reported to ameliorate impaired liver function in patients with advanced liver diseases through mobilization and proliferation of hepatic progenitor cells (HPCs). However, the underlying mechanisms remain unknown. We previously showed that G-CSF treatment increased the number of bone marrow (BM)-derived cells migrating to the fibrotic liver following repeated carbon tetrachloride (CCl4 ) injections into mice. In this study, we identified opioid growth factor receptor-like 1 (OGFRL1) as a novel BM cell-derived accelerator of fibrotic liver regeneration in response to G-CSF treatment. Endogenous Ogfrl1 was highly expressed in the hematopoietic organs such as the BM and spleen, whereas the liver contained a relatively small amount of Ogfrl1 mRNA. Among the peripheral blood cells, monocytes were the major sources of OGFRL1. Endogenous Ogfrl1 expression in both the peripheral blood monocytes and the liver was decreased following repeated CCl4 injections. An intrasplenic injection of cells overexpressing OGFRL1 into CCl4 -treated fibrotic mice increased the number of HPC and stimulated proliferation of hepatic parenchymal cells after partial resection of the fibrotic liver. Furthermore, overexpression of OGFRL1 in cultured HPC accelerated their differentiation as estimated by increased expression of liver-specific genes such as hepatocyte nuclear factor 4α, cytochrome P450, and fatty acid binding protein 1, although it did not affect the colony forming ability of HPC. These results indicate a critical role of OGFRL1 in the mobilization and differentiation of HPC in the fibrotic liver, and administration of OGFRL1-expressing cells may serve as a potential regenerative therapy for advanced liver fibrosis. Stem Cells 2019;37:89-101.

Is the T1/2N1 (≤3 nodes) category actually stage IIIA (TNM)/IIIa (Japanese classification) in patients with primary colorectal cancer?

The 5-year relapse-free survival rate (5Y-RFS) and the 5-year overall survival rate (5Y-OS) were calculated for 972 patients (stage I, 206 patients; stage II, 396 patients; stage III, 370 patients). We divided the stage III group into 259 patients with IIIa/N1 disease (≤3 positive nodes) and 111 patients with IIIb/N2 disease (≥4 positive nodes) according to the Japanese classification. The IIIa/N1 and IIIb/N2 categories were each subdivided into T1/2 (stage IIIa, 45 cases; IIIb, 9 cases) and ≥T3 (stage IIIa, 214 cases; IIIb, 102 cases) according to the TNM classification, and 5Y-RFS and 5Y-OS were compared between each subcategory and each group. The 5Y-RFS/5Y-OS values calculated for each stage were as follows: stage I, 94.0/90.7%; stage II, 80.5/81.1%; stage III, 63.5/65.7%. When stage IIIa was compared with IIIb, we obtained 67.9/72.0% for stage IIIa and 53.6% (p=0.001)/50.4% (p<0.001) for stage IIIb. For stage IIIa vs. IIIb in the ≥T3 category, we obtained 63.1/68.5% for stage IIIa and 51.9% (p=0.010)/49.0% (p=0.008) for stage IIIb. For stage IIIa vs. IIIb in the T1/2 category, we obtained 92.1/92.0% for stage IIIa and 72.9% (p=0.040)/63.5% (p=0.003) for stage IIIb. There were significant differences between T1/2 and ≥T3 within stage IIIa (p=0.001/p=0.009), but not within stage IIIb. These results suggest that the T1/2N1 category of colorectal cancer should be classified as a subcategory of stage IB/Ib rather than stage IIIA (TNM)/IIIa (Japanese classification).

Anal function-preserving subtotal intersphincteric resection/partial external sphincteric resection with hybrid 2-port hand-assisted laparoscopic surgery (Mukai's operation) for very low stage I rectal cancer: A case report.

A 62-year-old male patient underwent endoscopic mucosal resection (EMR). Additional hybrid 2-port hand-assisted laparoscopic surgery (HALS) (Mukai's operation) was performed for early rectal cancer located at the distal border of the rectum/below the peritoneal reflection (Rb) region [SM massive invasion/ly+/vertical margin (VM)X] via a small transverse incision, approximately 55 mm long, at the superior border of the pubic bone. After the pelvic floor muscles were dissected by laparoscopy-assisted manipulation, transanal subtotal intersphincteric resection (ISR) was performed under direct vision, securing a margin of more than 15 mm distal to the EMR scar. Partial external sphincteric resection (ESR) was also performed to obtain an adequate VM at the posterior region of the EMR scar. After bowel reconstruction, the layers were sutured transanally and a temporary covering colostomy was created. The resected specimen contained no residual tumor cells without lymph node metastasis. At 3 months after the operation, digital examination revealed good tonus of the anal muscles without stricture. The patient is currently undergoing rehabilitation of his anal sphincter muscles in preparation for the colostomy closure. In conclusion, subtotal ISR combined with partial ESR may decrease the need to perform Miles' operation for T1/2 stage I rectal cancer located at the distal border of the Rb region.

Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice.

Recent studies show that bone marrow (BM)-derived cells migrating into a dermal wound promote healing by producing collagen type I. However, their contribution to the repair process has not been fully verified yet. It is also unclear whether BM-derived cells participate in dermal fibrogenesis. We have addressed these issues using transgenic mice that harbor tissue-specific enhancer/promoter sequences of α2(I) collagen gene linked to either enhanced green fluorescent protein (COL/EGFP) or the luciferase (COL/LUC) reporter gene. Following dermal excision or subcutaneous bleomycin administration, a large number of EGFP-positive collagen-producing cells appeared in the dermis of COL/EGFP reporter mice. When wild-type mice were transplanted with BM cells from transgenic COL/EGFP animals and subjected to dermal excision, no EGFP-positive BM-derived collagen-producing cells were detected throughout the repair process. Luciferase assays of dermal tissues from COL/LUC recipient mice also excluded collagen production by BM-derived cells during dermal excision healing. In contrast, a limited but significant number of CD45-positive collagen-producing cells migrated from BM following bleomycin injection. These results indicate that resident cells in the skin are the major source of de novo collagen deposition in both physiological and pathological conditions, whereas BM-derived cells participate, in part, in collagen production during dermal fibrogenesis.

Two-stage treatment (Mukai's method) with hybrid 2-port HALS (Mukai's operation) for complete bowel obstruction by left colon cancer or rectal cancer.

During the initial emergency operation, a temporary loop colostomy (TLC) was constructed at the oral border of the region for subsequent radical resection. Then, radical surgery was performed by hybrid 2-port HALS (Mukai's operation) using the TLC as the hand access site. Left hemicolectomy was done in three patients, sigmoidectomy in two cases, low anterior resection in one case, and Hartmann's operation in one case. Radical surgery was not done in one patient with multiple distant metastases. The mean operating time was 3 h and 7 min (ranging from 1 h and 55 min to 3 h and 47 min), the mean blood loss was 146.4 ml (7-354 ml), the mean duration from TLC to HALS was 11.3 days (8-16 days), and the mean hospital stay after HALS was 13.9 days (9-20 days). Mild wound infection occurred postoperatively in 2/7 patients and ileus occurred in one patient. However, there was no anastomotic leakage/stricture or conversion to conventional laparotomy. These results suggest that 2-stage treatment (Mukai's method with Mukai's operation) is also applicable to large obstructing left colon or rectal cancers. This method is safe, less invasive, and achieves excellent results, including a good cosmetic outcome.

Efficacy of hybrid 2-port hand-assisted laparoscopic surgery (Mukai's operation) for patients with primary colorectal cancer.

In this study, a total of 108 patients with primary colorectal cancer who underwent hybrid 2-port hand-assisted laparoscopic surgery (HALS) were classified as 58 patients with colon cancer and 50 patients with rectal cancer. The mean operating time, mean blood loss, postoperative complications, and mean postoperative hospital stay were compared between the two groups. In patients who underwent colon cancer surgery, the mean operating time was 2 h and 26 min, the mean blood loss was 166.3 ml, and the postoperative complications were wound infection in 5/58 patients (8.6%), postoperative ileus in 3 patients (5.2%), and anastomotic stricture in 1 patient (1.7%). There was no anastomotic leakage and no conversion to conventional open laparotomy. The mean postoperative hospital stay was 12.6 days. In patients who underwent rectal cancer surgery, the mean operating time was 3 h and 38 min, the mean blood loss was 238.8 ml, and the postoperative complications consisted of wound infection in 6/50 patients (12.0%), anastomotic leakage in 3/35 patients (8.6%), anastomotic stricture in 3/47 patients (6.4%), postoperative ileus in 3/50 patients (6.0%), and conversion to conventional open laparotomy in 1/50 patients (2.0%). A covering stoma was constructed during surgery in 12/47 patients (25.5%). The mean postoperative hospital stay was 19.1 days. These results suggest that hybrid 2-port HALS (Mukai's operation) could become a standard method for the treatment of colorectal cancer, and that the long-term outcome should be compared in detail with that of standard laparotomy in the future.

Efficacy of 5-FU/LV plus CPT-11 as first-line adjuvant chemotherapy for stage IIIa colorectal cancer.

The aim of this study was to retrospectively evaluate the effect of adding CPT-11 to postoperative chemotherapy for stage III colorectal cancer. The subjects were 94 patients, including 60 in stage IIIa (or=4 positive nodes), who underwent curative resection. The clinical outcome was compared between patients receiving 5-FU/LV plus CPT-11 (FLC group) and patients receiving 5-FU/LV alone (FL group). The FLC group (54 patients) had a 3-year relapse-free survival (3Y-RFS) of 68.7%, a 5Y-RFS of 68.7% and a 5Y-OS of 67.1%, while the FL group (40 patients) had a 3Y-RFS of 67.5% (n.s.), a 5Y-RFS of 64.9% (n.s.), and a 5Y-OS of 77.3% (n.s.). There were no significant differences of these parameters between the two groups. For stage IIIa patients, the corresponding survival rates were 92.4, 92.4 and 90.9% in the FLC group (29 patients) vs. 64.5% (p=0.024), 61.1% (p=0.018), and 77.1% (n.s.) in the FL group (31 patients). For stage IIIb patients, the rates were 36.6, 36.6 and 24.8% in the FLC group (25 patients) vs. 77.8% (n.s.), 77.8% (n.s.), and 77.8% (n.s.) in the FL group (9 patients). These results suggest that the 3Y-RFS and 5Y-RFS of patients with stage IIIa colorectal cancer were significantly improved by adjuvant chemotherapy with 5-FU/LV plus CPT-11.

Negligible contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice.

BACKGROUND & AIMS: Recent studies have reported that bone marrow (BM)-derived cells migrating into fibrotic liver tissue exhibit a myofibroblast-like phenotype and may participate in the progression of liver fibrosis. However, their contribution to collagen production has not been fully verified yet. We revisited this issue by using 2 mechanistically distinct liver fibrosis models introduced into transgenic collagen reporter mice and their BM recipients. METHODS: BM of wild-type mice was replaced by cells obtained from transgenic animals harboring tissue-specific enhancer/promoter sequences of alpha2(I) collagen gene (COL1A2) linked to enhanced green fluorescent protein (EGFP) or firefly luciferase (LUC) gene. Liver fibrosis was introduced into those mice by repeated carbon tetrachloride injections or ligation of the common bile duct. Activation of COL1A2 promoter was assessed by confocal microscopic examination detecting EGFP signals and luciferase assays of liver homogenates. RESULTS: The tissue-specific COL1A2 enhancer/promoter was activated in hepatic stellate cells following a single carbon tetrachloride injection or during primary culture on plastic. A large number of EGFP-positive collagen-expressing cells were observed in liver tissue of transgenic COL1A2/EGFP mice in both liver fibrosis models. In contrast, there were few EGFP-positive BM-derived collagen-producing cells detected in fibrotic liver tissue of COL1A2/EGFP recipients. Luciferase assays of liver tissues from COL1A2/LUC-recipient mice further indicated that BM-derived cells produced little collagen in response to fibrogenic stimuli. CONCLUSIONS: By using a specific and sensitive experimental system, which detects exclusively BM-derived collagen-producing cells, we conclude an unexpectedly limited role of BM-derived cells in collagen production during hepatic fibrogenesis.

Curative resection by hybrid 2-port HALS in a patient with advanced cecal cancer invading the urinary bladder: a case report.

A 67-year-old woman was referred to our department for assessment of a tumor in the right lower abdomen. Advanced cecal cancer invading the urinary bladder was diagnosed, and laparoscopy assisted colorectal surgery (LACS)-hybrid 2-port hand-assisted laparoscopic surgery (HALS) was performed in February 2008. Intraoperative laparoscopic observation revealed direct invasion of the urinary bladder by the primary tumor, so an approximately 6-cm transverse suprapubic incision was made. Under direct vision through this incision, full-thickness partial cystectomy was performed to remove the tumor invading the bladder. Then D3 right hemicolectomy was performed under pneumoperitoneum. In this patient with advanced cecal cancer invading the bladder, we performed radical curative surgery by hybrid 2-port HALS, a minimally invasive procedure in which a 6-cm incision was made in addition to the hand access site and favorable results were obtained.

Hybrid 2-port hand-assisted laparoscopic surgery for the 2-stage treatment of a complete bowel obstruction by distal sigmoid colon cancer: a case report.

In July 2008, a 40-year-old man presented to his local physician with diffuse abdominal pain and severe abdominal distension. Impending bowel rupture due to colonic obstruction was strongly suspected. Complete obstruction of the distal sigmoid colon by a tumor was diagnosed, and emergency surgery was performed. A sigmoid colon loop colostomy was created within the range of subsequent resection to relieve the obstruction. After his general condition had improved and the risks were assessed, curative resection including removal of the stoma was performed by hybrid 2-port hand-assisted laparoscopic surgery. The tumor showed invasion of the serosa without lymph node metastasis, and its pathological diagnosis was stage II. Postoperatively, mild wound infection occurred at the hand access site (stoma), but it resolved with conservative treatment, and the patient was discharged on postoperative day 13. This case is reported here because of the good results.

Trans-anal reinforcing sutures after double stapling for lower rectal cancer: report of two cases.

To safely avoid the construction of a covering stoma in patients with advanced lower rectal cancer undergoing laparoscopy assisted colorectal surgery (LACS), we added circumferential manual reinforcing sutures via the transanal approach at the site of mechanical anastomosis. In June 2008, LACS was performed for a tumor of 6 cm in longer diameter in the Rb region of the lower rectum approximately 5 cm from the anal verge. After intraperitoneal coloproctal anastomosis was performed in the pelvis by the double stapling technique (DST), reinforcement was provided by manual trans-anal suturing (trans-anal reinforcing sutures: TARS). A covering stoma was constructed because this was a high-risk case. Complications such as mild wound infection and stoma trouble occurred, and the patient was discharged after conservative therapy. In June 2008, LACS was performed for a tumor of 5 cm in longer diameter in the Ra region of the lower rectum approximately 7 cm from the anal verge. After intraperitoneal colorectal anastomosis was performed in the pelvis by DST, TARS were added to avoid a covering stoma. Minor leakage occurred postoperatively, but this was controlled conservatively and the patient was discharged. In patients having surgical treatment of advanced lower rectal cancer, good results were obtained by adding circumferential reinforcing sutures via the trans-anal approach at the site of ultra-low anastomosis after DST.