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Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P < 0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (CRT) for clinical Stage I (T1N0M0) esophageal cancer.Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T1a) in 23 and submucosal cancer (T1b) in 40. CRT consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions.The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T1a and T1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T1a and T1b were 84.4% and 50.5%, respectively (p0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G4: 1; G5: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients.We confirmed that patients with T1N0M0 esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive CRT, and the survival rates were equivalent to those of previous reports of surgery.

We analyzed response, side effects, and local control rates of a multimodal treatment consisting of intraarterial infusion chemotherapy (IAIC) and radiotherapy with or without surgery for patients with locally advanced or recurred breast cancer. Thirty-three patients, clinically diagnosed as stage IIB in 1, IIIA in 2, IIIB in 12, IV in 18, were treated from 1991 to 1998. Twenty-five were primary and eight were recurrent cases after surgery. IAIC started as initial treatment up to three times maximum. In most cases, doxorubicin 50 mg, cisplatin 50 mg, and mitomycin 10 mg were infused in the subclavian and/or internal mammary artery. After IAIC, patients in primary cases underwent radical mastectomy or breast conservation surgery, after radiotherapy at a total dose of 50 Gy/25 fractions/5 weeks with a boost of 10 Gy. In recurrent cases, a full dose of radiotherapy was delivered. Clinical objective and complete response rates were 78% and 9% after IAIC. Despite a high rate of residual positive margin (67%) or clinically residual carcinoma, local recurrence developed only in 2 patients (6%) and local control rates at 5 years were calculated as 89%. Bone marrow suppression was frequent, and skin vesiculation (15%) and ulceration (9%) were experienced after IAIC. Skin ulcer (6%), brachial plexus neuropathy (3%), and radiation pneumonitis (3%) occurred as late toxicity. IAIC was effective as an induction treatment and radiotherapy played a role of local control for patients with locally advanced or recurrent breast cancer.

Selenium (Se) is an essential trace element in humans. Patients receiving long-term parenteral nutrition (PN) are at risk for Se deficiency. We investigated changes in Se levels and glutathione peroxidase (GSH-Px) activity in serum and tissue (red blood cells, RBC) in addition to urinary excretion of Se in patients receiving long-term PN with and without Se supplementation. In patients without Se supplementation, both Se levels and GSH-Px activity in serum decreased with duration of PN. The serum Se levels were below the lower limits of the control values in 19 of 33 patients (58%) who received PN for less than 1 mo. Conversely, RBC GSH-Px activity remained at a sufficient level in 9 of 12 patients (75%) who received PN for 3-6 mo. The RBC Se levels in all of these patients were lower than the control levels. Urinary Se concentrations were significantly correlated with serum Se concentrations by linear regression analysis (r = 0.707, P0.05). In patients with Se supplementation, urinary Se concentrations increased exponentially with increases in serum Se levels. These findings indicate that a time lag precedes the decrease in levels of serum Se, RBC Se, serum GSH-Px, and RBC GSH-Px in patients without Se supplementation and the increase in excretion of urinary Se in patients with Se supplementation. The monitoring of not only serum Se levels but also RBC GSH-Px activity and urinary Se levels is required for optimal Se supplementation during long-term PN.

We applied intraoperative radiotherapy (IORT) to the esophageal carcinoma in an attempt to prevent abdominal lymph node recurrence, and retrospectively studied patterns of failure and controllability of abdominal lymph nodes in patients treated with or without IORT. Between July 1986 and October 1997, 81 patients with radically resected esophageal carcinoma, aged 42-76 years (mean 61), were divided into two groups, the IORT group (39 patients) and the non-IORT group (42 patients). All patients except two, who received transhiatal esophagectomy for superficial carcinoma, underwent subtotal esophagectomy with thoracic and abdominal with/without cervical lymphadenectomy. Fourteen patients underwent only surgical resection, and the remaining 67 patients received radiotherapy to the mediastinum post-operatively (40-50 Gy/20-25 Fr/4-5 W) in 37 and preoperatively (44 Gy/40 Fr/4 W) in 30 patients. Preoperative irradiation was performed as a neoadjuvant chemoradiotherapy consisting of two courses of cisplatin (each patient received 80-100 mg, mean 60 mg m(-2), day 1, bolus injection) and 5-fluorouracil (each patient received 500-1000 mg day(-1), mean 400 mg m(-2), days 1-4, continuous infusion). The target volume of IORT encompassed the upper abdominal lymph node area including lymph node groups of right/left cardia, left gastric artery, celiac artery and abdominal para-aorta. A single dose of high-energy electrons (9-12 MeV) of 20-23 Gy, prescribed to the 90% isodose curve, was delivered. Treatment for the abdominal lymphatic system was classified into four categories: surgery alone in 30 patients, surgery with chemotherapy in 12, surgery with IORT in 15, surgery with chemotherapy and IORT in 24. There were no complications related to IORT. Forty patients (49%) had recurring carcinoma: in the lymph nodes (36%), in distant organs (27%) and locally (6%). The incidence of lymph node metastasis was 29% in the neck, 32% in the mediastinum, and 27% in the abdomen. Abdominal lymph node recurrence in the IORT group was less frequent than in the non-IORT group (p=0.048). In particular, 24 patients treated with a combination of surgery, chemotherapy and IORT had no recurrence in the abdominal lymphatic system. The overall median survival was 46 months, the survival at 1, 3, and 5 years being 85%, 52%, and 44% respectively. However, there was no difference in survival between the IORT group and the non-IORT group. The IORT for the abdominal lymphatic system was feasible for reduction of the rate of abdominal lymphatic recurrence without survival benefit in this study. This retrospective finding should be confirmed by a prospective randomized study.

Purpose: This retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma. Methods and Materials: Sixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m 2 , day 1, bolus; 5-FU: 400 mg/m 2 , day 1–4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. Results: In the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group ( p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group ( p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/ protocol group. Conclusion: The chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.

Purpose: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. Materials and Methods: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80–100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500–1000 mg/body/day, mean: 400 mg/m2, Days 1–4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60–70 Gy for Tis, T1 and 65–75 Gy for T2–T4 tumor with high-dose–rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. Results: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the ’esophagus conservation’ was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). Conclusion: Our results demonstrated that almost all early disease (Stage 0–I) and about half of advanced disease (Stage II–III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.

We report herein the case of a women receiving tamoxifen therapy for breast cancer who developed vaginal bleeding, subsequently found to be caused by unusual endometrial polyps. Upon presentation, ultrasonography and magnetic resonance imaging (MRI) demonstrated a tumor within the uterus. A hysterectomy was performed, and macroscopic examination showed polyp-like lesions of the uterus. Histologically, these polyps demonstrated cystically dilated glands and stromal proliferation, and were diagnosed as endometrial polyps. Although tamoxifen has few side effects, any signs or symptoms of gynecological abnormalities should be carefully evaluated in patients on long-term tamoxifen therapy.

To develop a criterion to evaluate architectural changes of the subcutaneous tissue layer around the breast, 120 patients with histologically proven tumors were studied as to ultrasonographical delineation of the superficial layer (SL) of the superficial fascia. Breast ultrasonography was performed using an electronic-linear scanner with a 5.0 MHz probe. When SL was identified over the tumor, it was classified into 3 types: flat, disrupted, and convergent types. SL was identified in 106 patients (88%). Forty-six were evaluated to be flat type, and 41 (89%) of them had benign tumors. The remaining 60 were subdivided into either disrupted (n = 44) or convergent type (n = 16); 53 (88%) of these 60 cases had cancerous lesions. Histologically, inward retraction of SL was the most common pattern in breast cancer. Thus, the ultrasonographic pattern of SL reflects the histological findings and can be a useful clue to differentiate benign lesions from cancerous ones.

Anomalies of the biliary ductal system are not uncommon, and their clinical significance is variable. We present herein the case of a 70-year-old Japanese woman found to have an anomalous duplicated cystic duct, which is an extremely rare congenital anomaly. Intraoperative delineation of the anomaly by real-time cholangiograms assisted us in being able to subsequently perform a safe cholecystectomy. This case serves to demonstrate the importance of being aware of the possibility of potential biliary variations in order to avoid ductal injuries during biliary surgery.

The methods and results of treatment for cancer of the cervical esophagus differ from those for cancer of the thoracic esophagus. Our objective was to retrospectively review the outcome for cervical esophageal cancer patients treated with radiotherapy. Twenty-seven patients with carcinoma of the cervical esophagus treated with definitive radiotherapy from 1988 to 2002 were enrolled in the study. Clinical stage (UICC 1997) was stage I in five, II in six, III in 12 and IV in four. Concurrent head and neck malignancy was found in six patients (22%). The mean radiation dose was 66 Gy. Concurrent chemotherapy (cisplatin and 5-fluorouracil) was performed in 23 patients. The actuarial overall survival rates at 1, 3 and 5 years were 55.6%, 37.9% and 37.9%, respectively, with a median survival of 13.9 months. In the patients with stage I, the 3-year and 5-year survival rates were 75% and 75%, respectively. With univariate analysis, only two of the possible prognostic factors were found to actually influence survival: performance status (p < 0.01) and tumor length (p < 0.01). The survival of patients with cervical esophageal cancer remains poor. It is thought that organ preservation is possible by definitive chemoradiation for early cancer.

Vascular lesions of the duodenum, including hemangioma, are rare causes of gastrointestinal bleeding. We herein describe a 52-year-old woman with a solitary cavernous hemangioma of the duodenum that caused chronic gastrointestinal bleeding. Repeated upper gastrointestinal endoscopy and a barium meal study revealed a solitary vascular tumor in the fourth portion of the duodenum, although the initial investigations including selective angiography were unsuccessful. A wedge resection of the duodenum was performed and microscopical examination showed a cavernous hemangioma. Vascular lesions should therefore also be considered in the differential diagnosis of patients with gastrointestinal bleeding of unknown origin.

A 39-year-old woman came to us complaining of severe anemia (hemoglobin: 2.3 g/dl) and a painful right breast that was entirely occupied by an ulcerative, foul-smelling tumor approximately 20 cm in maximum dimension. The tumor, which was determined to be mucinous adenocarcinoma at biopsy, had invaded the chest wall with multiple lung metastases (T4cN2M1 stage IV). After a blood transfusion, the patient received the following multimodal treatment: concurrent chemoradiotherapy (50 Gy), intraarterial infusion chemotherapy consisting of doxorubicin 50 mg, mitomycin-C 10 mg, and cisplatin 50 mg, and skin graft surgery. After intraarterial infusion chemotherapy, the fungating tumor disappeared. The patient experienced a relapse of right pleural effusion 2 years later and received multimodal treatment. Now, March 30, 2000, the patient is doing well without local recurrence, 8 years after her first admission. The combination of intraarterial infusion chemotherapy and radiotherapy plays a role in successful treatment of extensive local disease of the breast.

We have been treating patients with operable thoracic esophageal cancer according to our own protocol. It includes the initial concurrent chemoradiotherapy (CRT) followed by continuous CRT or surgery. Patients with good response to initial chemoradiotherapy were allowed to continue chemoradiotherapy, whereas the others were treated with surgery. However, there were two cases which showed discrepancies in the clinicopathological response. Both patients received initial chemoradiotherapy, including two courses of cisplatin (100-120 mg), 5-fluorouracil (750-1000 mg for 4 days) and radiation (44-50 Gy). On completion of the initial chemoradiotherapy, all diagnostic imaging modalities including barium swallow, esophagoscopy, endoscopic ultrasonography and thoracic computed tomography strongly implicated residual tumor with a reduction rate of 40-50%. The patients underwent radical esophagectomy 15-20 days after initial chemoradiotherapy. Pathological specimens only revealed thickening of the esophageal wall due to inflammatory change without residual carcinoma. These facts suggest the current limitations of diagnostic images in evaluating the response to chemoradiotherapy.

We investigated results for thoracic T3-T4 esophageal squamous cell carcinoma in two strategies. The protocol group (46 patients) consisted of neoadjuvant chemoradiotherapy (44 Gy, CDDP, 5-FU), followed by either definitive radiotherapy (total 70 Gy) for responders or surgery for non-responders. The surgery group (26 patients) underwent esophagectomy with regional lymph node dissection. Nineteen of them received postoperative radiotherapy. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. In the protocol group, 23 patients underwent radical surgery after neoadjuvant chemoradiotherapy and the remaining 23 underwent definitive radiotherapy. The rates of recurrence were 64% in the protocol group, and 62% in the surgery group. Overall 3- and 5-year survival rates were 48% and 31% in the protocol group compared to those of 30% and 30% in the surgery group. The rate of theesophagus conservationwas 39% in the protocol group. There was no mortality in either group. Our protocol had at least comparable prognostic values with historical conventional surgery, and was excellent in having feasibility for organ preservation.

The factors influencing the healing process of pancreaticojejunostomy (P-J) following pancreaticoduodenectomy (PD) are still ill defined, allowing the recommendation of various anastomotic methods. We conduced a prospective study to determine the risk factors influencing the protracted healing of P-J, examining 100 consecutive patients who underwent PD followed by P-J, performed as an end-to-side “mucosa-to-mucosa” anastomosis using vertical mattress sutures (VMS method). Protracted healing of P-J was classified as either peripancreatic sepsis (PPS), defined as prolonged suppurative discharge of less than 50 ml a day from the drain beneath the P-J for more than 1 week; or a pancreatic fistula (PF), defined as prolonged discharge of more than 50 ml a day with a high amylase content (>1000 IU) for more than 1 week. There were 80 patients with a malignant neoplasm, and 20 with benign disease. The overall incidence of healing problems following P-J was 9%, which included 6 patients (6%) with PPS and 3 (3%) with PF. Apart from an advanced age of more than 70 years, none of the patients' characteristics or postoperative complications influenced the healing of P-J. The type of reconstruction, an anastomotic stent, the duct size, and a “soft” pancreas were not risk factors either. In conclusion, no factors, apart from the age or any special problem of an individual patient, influenced the dehiscence of P-J when the VMS method was used after PD.

This study was undertaken to determine whether short-term continuous epidural analgesia using morphine would relieve pain after laparoscopic cholecystectomy. The authors retrospectively reviewed the clinical data of 182 cases who had undergone a laparoscopic cholecystectomy. These cases were divided into four groups according to their anesthetic modes as follows: a control group with general anesthesia only (n = 37); group I, general anesthesia combined with one shot of epidural morphine (n = 78); and group II, general anesthesia combined with continuous epidural analgesia using morphine (IIa for 12 h (n = 33); IIb for 8 h (n = 34)). The pain score on a four-category verbal scale and the frequency of analgesic use were investigated. There were no differences in the background characteristics of the patients among the groups, except for the duration of surgery (I vs IIa; P = 0.006). The pain scores were significantly different between the control group and the other groups. The frequency of analgesic use in the control group was also significantly higher than in the other groups. A tendency toward a higher frequency of analgesic use in group I, compared with that in groups IIa and IIb, was observed. These findings thus suggest that short-term continuous epidural analgesia using morphine can effectively relieve postoperative pain after a laparoscopic cholecystectomy.

A prospective, randomized study was conducted to determine whether simultaneous infusion of lipid emulsion with an amino acid-dextrose-electrolyte solution would reduce the incidence of thrombophlebitis (TP) during postoperative peripheral parenteral nutrition (PPN). Thirty patients who had undergone gastric resection for adenocarcinoma were randomly divided into two groups according to whether they were infused with 10% lipid emulsion (group A) or 5% glucose solution (group B) simultaneously with the amino acid-glucose solutions. The total osmolarity of the infusion solutions in each group was 853 mOsm/l. The incidence of complications due to TP, namely, redness and/or edema beneath the cannula insertion site and/or pain, was investigated. There were no differences in the background characteristics of the patients in groups A and B, except regarding concurrent resection of other organs (P = 0.03). The incidence of edema in group A was significantly lower than in group B on postoperative days 2 and 4, although there was no difference in the incidence of redness and pain between the two groups. These findings suggest that the simultaneous infusion of lipid emulsion has a preventive effect against TP during postoperative PPN, and may be a practical means of providing PPN after gastrointestinal surgery.

In the period from January 1985 to May 1987, 68 patients with palpable breast cancers were studied to compare the size on ultrasonography with the size of the cut-surface of the resected specimen. Both the width (mediolateral size) and height (size in depth) were delineated as smaller on ultrasonography than on the cut-surface of resected specimens. The difference in size between ultrasonography and resected specimen was greater for the width than for the height. These results can explain why breast cancer has a greater ratio of height to width on ultrasonography. The ratio of the width on palpation to that on ultrasonography was also evaluated. These ratios proved to be useful in differentiating breast cancer from benign lesions.

A multivariate probit analysis was used to develop a prognostic scoring system known as the Prognostic Index (PI), which consisted of age, pulse rate, blood urea nitrogen, serum albumin, serum cholesterol and serum potassium. This PI accurately predicted the severity and mortality of 83 surgical patients with septic shock caused by gastrointestinal diseases, who were admitted to Tenri Hospital, Nara, Japan from 1975 to 1981 (internal check), and also that of 25 other patients, examined from 1982 to 1983 (external check). As the prognostic predictive model provides a prompt and easy prediction of how severe the patients' state is, it has proved to be very useful to our surgical staff for managing critically ill patients.

Three cases of obstruction of the afferent loop following a Billroth II type gastrectomy were preoperatively detected by ultrasonography. The obstructions in the 3 patients were caused by volvulus, internal herniation and recurrence of gastric cancer, respectively. The important US findings which helped diagnose this condition were a dilated intestinal loop without gas echo in the upper abdominal cavity and echo lucent swelling of the pancreas. Ultrasonography is very useful for the early and easy detection of this life-threatening condition which requires immediate surgery.

Total pancreatectomy was performed for carcinoma of the head of the pancreas associated with multiple anomalies in the peripancreatic region and of the pancreas. The anomalies were preduodenal portal vein, annular pancreas with agenesis of the dorsal pancreas, left-sided gallbladder, polysplenia and high mobile right colon. The surgical implications of pancreatectomy for such anatomical abnormalities, especially preduodenal portal vein, and the usefulness of ultrasonography for the preoperative evaluation are given attention.